Sina Jostes, Chiara Vardabasso, Joanna Dong, Saul Carcamo, Rajendra Singh, Robert Phelps, Austin Meadows, Elena Grossi, Dan Hasson, Emily Bernstein
High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes SRCAP and P400-TIP60 in melanoma remains unclear. Here, we show that individual subunit depletion of SRCAP, P400, and VPS72 (YL1) results in not only the loss of H2A.Z deposition into chromatin but also a reduction of H4 acetylation in melanoma cells. This loss of H4 acetylation is particularly found at the promoters of cell cycle genes directly bound by H2A.Z and its chaperones, suggesting a coordinated regulation between H2A.Z deposition and H4 acetylation to promote their expression. Knockdown of each of the three subunits downregulates E2F1 and its targets, resulting in a cell cycle arrest akin to H2A.Z depletion. However, unlike H2A.Z deficiency, loss of the shared H2A.Z chaperone subunit YL1 induces apoptosis. Furthermore, YL1 is overexpressed in melanoma tissues, and its upregulation is associated with poor patient outcome. Together, these findings provide a rationale for future targeting of H2A.Z chaperones as an epigenetic strategy for melanoma treatment.
{"title":"H2A.Z chaperones converge on E2F target genes for melanoma cell proliferation.","authors":"Sina Jostes, Chiara Vardabasso, Joanna Dong, Saul Carcamo, Rajendra Singh, Robert Phelps, Austin Meadows, Elena Grossi, Dan Hasson, Emily Bernstein","doi":"10.1101/gad.351318.123","DOIUrl":"10.1101/gad.351318.123","url":null,"abstract":"<p><p>High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes SRCAP and P400-TIP60 in melanoma remains unclear. Here, we show that individual subunit depletion of <i>SRCAP</i>, <i>P400</i>, and <i>VPS72</i> (YL1) results in not only the loss of H2A.Z deposition into chromatin but also a reduction of H4 acetylation in melanoma cells. This loss of H4 acetylation is particularly found at the promoters of cell cycle genes directly bound by H2A.Z and its chaperones, suggesting a coordinated regulation between H2A.Z deposition and H4 acetylation to promote their expression. Knockdown of each of the three subunits downregulates E2F1 and its targets, resulting in a cell cycle arrest akin to H2A.Z depletion. However, unlike H2A.Z deficiency, loss of the shared H2A.Z chaperone subunit YL1 induces apoptosis. Furthermore, YL1 is overexpressed in melanoma tissues, and its upregulation is associated with poor patient outcome. Together, these findings provide a rationale for future targeting of H2A.Z chaperones as an epigenetic strategy for melanoma treatment.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"336-353"},"PeriodicalIF":7.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuel Ares, Haller Igel, Sol Katzman, John P Donohue
Rare, full-length circular intron RNAs distinct from lariats have been reported in several species, but their biogenesis is not understood. We envisioned and tested a hypothesis for their formation using Saccharomyces cerevisiae, documenting full-length and novel processed circular RNAs from multiple introns. Evidence implicates a previously undescribed catalytic activity of the intron lariat spliceosome (ILS) in which the 3'-OH of the lariat tail (with optional trimming and adenylation by the nuclear 3' processing machinery) attacks the branch, joining the intron 3' end to the 5' splice site in a 3'-5' linked circle. Human U2 and U12 spliceosomes produce analogous full-length and processed circles. Postsplicing catalytic activity of the spliceosome may promote intron transposition during eukaryotic genome evolution.
{"title":"Intron lariat spliceosomes convert lariats to true circles: implications for intron transposition.","authors":"Manuel Ares, Haller Igel, Sol Katzman, John P Donohue","doi":"10.1101/gad.351764.124","DOIUrl":"10.1101/gad.351764.124","url":null,"abstract":"<p><p>Rare, full-length circular intron RNAs distinct from lariats have been reported in several species, but their biogenesis is not understood. We envisioned and tested a hypothesis for their formation using <i>Saccharomyces cerevisiae</i>, documenting full-length and novel processed circular RNAs from multiple introns. Evidence implicates a previously undescribed catalytic activity of the intron lariat spliceosome (ILS) in which the 3'-OH of the lariat tail (with optional trimming and adenylation by the nuclear 3' processing machinery) attacks the branch, joining the intron 3' end to the 5' splice site in a 3'-5' linked circle. Human U2 and U12 spliceosomes produce analogous full-length and processed circles. Postsplicing catalytic activity of the spliceosome may promote intron transposition during eukaryotic genome evolution.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"322-335"},"PeriodicalIF":7.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zuolian Shen, Yifan Wu, Asit Manna, Chongil Yi, Bradley R. Cairns, Kimberley J. Evason, Mahesh B. Chandrasekharan, Dean Tantin
The transcription factor Oct4/Pou5f1 is a component of the regulatory circuitry governing pluripotency and is widely used to induce pluripotency from somatic cells. Here we used domain swapping and mutagenesis to study Oct4's reprogramming ability, identifying a redox-sensitive DNA binding domain, cysteine residue (Cys48), as a key determinant of reprogramming and differentiation. Oct4 Cys48 sensitizes the protein to oxidative inhibition of DNA binding activity and promotes oxidation-mediated protein ubiquitylation. Pou5f1C48S point mutation has little effect on undifferentiated embryonic stem cells (ESCs) but upon retinoic acid (RA) treatment causes retention of Oct4 expression, deregulated gene expression, and aberrant differentiation. Pou5f1C48S ESCs also form less differentiated teratomas and contribute poorly to adult somatic tissues. Finally, we describe Pou5f1C48S (Janky) mice, which in the homozygous condition are severely developmentally restricted after E4.5. Rare animals bypassing this restriction appear normal at birth but are sterile. Collectively, these findings uncover a novel Oct4 redox mechanism involved in both entry into and exit from pluripotency.
{"title":"Oct4 redox sensitivity potentiates reprogramming and differentiation","authors":"Zuolian Shen, Yifan Wu, Asit Manna, Chongil Yi, Bradley R. Cairns, Kimberley J. Evason, Mahesh B. Chandrasekharan, Dean Tantin","doi":"10.1101/gad.351411.123","DOIUrl":"https://doi.org/10.1101/gad.351411.123","url":null,"abstract":"The transcription factor Oct4/Pou5f1 is a component of the regulatory circuitry governing pluripotency and is widely used to induce pluripotency from somatic cells. Here we used domain swapping and mutagenesis to study Oct4's reprogramming ability, identifying a redox-sensitive DNA binding domain, cysteine residue (Cys48), as a key determinant of reprogramming and differentiation. Oct4 Cys48 sensitizes the protein to oxidative inhibition of DNA binding activity and promotes oxidation-mediated protein ubiquitylation. <em>Pou5f1</em><sup><em>C48S</em></sup> point mutation has little effect on undifferentiated embryonic stem cells (ESCs) but upon retinoic acid (RA) treatment causes retention of Oct4 expression, deregulated gene expression, and aberrant differentiation. <em>Pou5f1</em><sup><em>C48S</em></sup> ESCs also form less differentiated teratomas and contribute poorly to adult somatic tissues. Finally, we describe <em>Pou5f1</em><sup><em>C48S</em></sup> (<em>Janky</em>) mice, which in the homozygous condition are severely developmentally restricted after E4.5. Rare animals bypassing this restriction appear normal at birth but are sterile. Collectively, these findings uncover a novel Oct4 redox mechanism involved in both entry into and exit from pluripotency.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"10 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wen Xiao, Reem Halabi, Chia-Ho Lin, Mohammad Nazim, Kyu-Hyeon Yeom, Douglas L. Black
Synaptic function in neurons is modulated by local translation of mRNAs that are transported to distal portions of axons and dendrites. The metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is broadly expressed across cell types, almost exclusively as a nuclear long noncoding RNA. We found that in differentiating neurons, a portion of Malat1 RNA redistributes to the cytoplasm. Depletion of Malat1 using antisense oligonucleotides (ASOs) stimulates the expression of particular pre- and postsynaptic proteins, implicating Malat1 in their regulation. Neuronal Malat1 is localized in puncta of both axons and dendrites that costain with Staufen1 protein, similar to neuronal RNA granules formed by locally translated mRNAs. Ribosome profiling of cultured mouse cortical neurons identified ribosome footprints within a 5′ region of Malat1 containing short open reading frames. The upstream-most reading frame (M1) of the Malat1 locus was linked to the GFP-coding sequence in mouse embryonic stem cells. When these gene-edited cells were differentiated into glutamatergic neurons, the M1-GFP fusion protein was expressed. Antibody staining for the M1 peptide confirmed its presence in wild-type neurons and showed that M1 expression was enhanced by synaptic stimulation with KCl. Our results indicate that Malat1 serves as a cytoplasmic coding RNA in the brain that is both modulated by and modulates synaptic function.
{"title":"The lncRNA Malat1 is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons","authors":"Wen Xiao, Reem Halabi, Chia-Ho Lin, Mohammad Nazim, Kyu-Hyeon Yeom, Douglas L. Black","doi":"10.1101/gad.351557.124","DOIUrl":"https://doi.org/10.1101/gad.351557.124","url":null,"abstract":"Synaptic function in neurons is modulated by local translation of mRNAs that are transported to distal portions of axons and dendrites. The metastasis‐associated lung adenocarcinoma transcript 1 (<em>MALAT1</em>) is broadly expressed across cell types, almost exclusively as a nuclear long noncoding RNA. We found that in differentiating neurons, a portion of <em>Malat1</em> RNA redistributes to the cytoplasm. Depletion of <em>Malat1</em> using antisense oligonucleotides (ASOs) stimulates the expression of particular pre- and postsynaptic proteins, implicating <em>Malat1</em> in their regulation. Neuronal <em>Malat1</em> is localized in puncta of both axons and dendrites that costain with Staufen1 protein, similar to neuronal RNA granules formed by locally translated mRNAs. Ribosome profiling of cultured mouse cortical neurons identified ribosome footprints within a 5′ region of <em>Malat1</em> containing short open reading frames. The upstream-most reading frame (M1) of the <em>Malat1</em> locus was linked to the GFP-coding sequence in mouse embryonic stem cells. When these gene-edited cells were differentiated into glutamatergic neurons, the M1-GFP fusion protein was expressed. Antibody staining for the M1 peptide confirmed its presence in wild-type neurons and showed that M1 expression was enhanced by synaptic stimulation with KCl. Our results indicate that <em>Malat1</em> serves as a cytoplasmic coding RNA in the brain that is both modulated by and modulates synaptic function.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"146 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Malat1 (metastasis-associated lung adenocarcinoma transcript 1) long noncoding RNA is highly and broadly expressed in mammalian tissues, accumulating in the nucleus where it modulates expression and pre-mRNA processing of many protein-coding genes. In this issue of Genes & Development, Xiao and colleagues (doi:10.1101/gad.351557.124) report that a significant fraction of Malat1 transcripts in cultured mouse neurons are surprisingly exported from the nucleus. These transcripts are packaged with Staufen proteins in RNA granules and traffic down the lengths of neurites. They then can be released in a stimulus-dependent manner to be locally translated into a microprotein that alters neuronal gene expression patterns.
{"title":"An unexpected path for Malat1 in neurons: trafficking out of the nucleus for translation","authors":"Bradley W. Wright, Jeremy E. Wilusz","doi":"10.1101/gad.351820.124","DOIUrl":"https://doi.org/10.1101/gad.351820.124","url":null,"abstract":"The Malat1 (metastasis-associated lung adenocarcinoma transcript 1) long noncoding RNA is highly and broadly expressed in mammalian tissues, accumulating in the nucleus where it modulates expression and pre-mRNA processing of many protein-coding genes. In this issue of <em>Genes & Development</em>, Xiao and colleagues (doi:10.1101/gad.351557.124) report that a significant fraction of Malat1 transcripts in cultured mouse neurons are surprisingly exported from the nucleus. These transcripts are packaged with Staufen proteins in RNA granules and traffic down the lengths of neurites. They then can be released in a stimulus-dependent manner to be locally translated into a microprotein that alters neuronal gene expression patterns.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"9 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas Nuechterlein, Allison Shelbourn, Frank Szulzewsky, Sonali Arora, Michelle Casad, Siobhan Pattwell, Leyre Merino-Galan, Erik Sulman, Sumaita Arowa, Neriah Alvinez, Miyeon Jung, Desmond Brown, Kayen Tang, Sadhana Jackson, Stefan Stoica, Prashant Chittaboina, Yeshavanth K. Banasavadi-Siddegowda, Hans-Georg Wirsching, Nephi Stella, Linda Shapiro, Patrick Paddison, Anoop P. Patel, Mark R. Gilbert, Zied Abdullaev, Kenneth Aldape, Drew Pratt, Eric C. Holland, Patrick J. Cimino
Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR–Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominate PDE10A as a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro. Cell culture analysis showed that decreased Pde10a expression led to increased PI3K/AKT signaling in a Pten-independent manner, a response blocked by selective PI3K inhibitors. Single-nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation, further showed that Pde10a suppression was associated with a proneural-to-mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. Our results indicate that glioblastoma patients harboring PDE10A loss have worse outcomes and potentially increased sensitivity to PI3K inhibition.
{"title":"Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype","authors":"Nicholas Nuechterlein, Allison Shelbourn, Frank Szulzewsky, Sonali Arora, Michelle Casad, Siobhan Pattwell, Leyre Merino-Galan, Erik Sulman, Sumaita Arowa, Neriah Alvinez, Miyeon Jung, Desmond Brown, Kayen Tang, Sadhana Jackson, Stefan Stoica, Prashant Chittaboina, Yeshavanth K. Banasavadi-Siddegowda, Hans-Georg Wirsching, Nephi Stella, Linda Shapiro, Patrick Paddison, Anoop P. Patel, Mark R. Gilbert, Zied Abdullaev, Kenneth Aldape, Drew Pratt, Eric C. Holland, Patrick J. Cimino","doi":"10.1101/gad.351350.123","DOIUrl":"https://doi.org/10.1101/gad.351350.123","url":null,"abstract":"Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR–Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominate <em>PDE10A</em> as a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro. Cell culture analysis showed that decreased Pde10a expression led to increased PI3K/AKT signaling in a Pten-independent manner, a response blocked by selective PI3K inhibitors. Single-nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation, further showed that Pde10a suppression was associated with a proneural-to-mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. Our results indicate that glioblastoma patients harboring <em>PDE10A</em> loss have worse outcomes and potentially increased sensitivity to PI3K inhibition.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"56 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140534304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian Freie, Patrick A. Carroll, Barbara J. Varnum-Finney, Erin L. Ramsey, Vijay Ramani, Irwin Bernstein, Robert N. Eisenman
Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently acquire point mutations in the MYC phosphodegron, including at threonine 58 (T58), where phosphorylation permits binding via the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal cell physiology, we introduced an alanine mutation at T58 (T58A) into the endogenous c-Myc locus in the mouse germline. While MYC-T58A mice develop normally, lymphomas and myeloid leukemias emerge in ∼60% of adult homozygous T58A mice. We found that primitive hematopoietic progenitor cells from MYC-T58A mice exhibit aberrant self-renewal normally associated with hematopoietic stem cells (HSCs) and up-regulate a subset of MYC target genes important in maintaining stem/progenitor cell balance. In lymphocytes, genomic occupancy by MYC-T58A was increased at all promoters compared with WT MYC, while genes differentially expressed in a T58A-dependent manner were significantly more proximal to MYC-bound enhancers. MYC-T58A lymphocyte progenitors exhibited metabolic alterations and decreased activation of inflammatory and apoptotic pathways. Our data demonstrate that a single point mutation stabilizing MYC is sufficient to skew target gene expression, producing a profound gain of function in multipotential hematopoietic progenitors associated with self-renewal and initiation of lymphomas and leukemias.
{"title":"A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies","authors":"Brian Freie, Patrick A. Carroll, Barbara J. Varnum-Finney, Erin L. Ramsey, Vijay Ramani, Irwin Bernstein, Robert N. Eisenman","doi":"10.1101/gad.351292.123","DOIUrl":"https://doi.org/10.1101/gad.351292.123","url":null,"abstract":"Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently acquire point mutations in the MYC phosphodegron, including at threonine 58 (T58), where phosphorylation permits binding via the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal cell physiology, we introduced an alanine mutation at T58 (T58A) into the endogenous <em>c-Myc</em> locus in the mouse germline. While MYC-T58A mice develop normally, lymphomas and myeloid leukemias emerge in ∼60% of adult homozygous T58A mice. We found that primitive hematopoietic progenitor cells from MYC-T58A mice exhibit aberrant self-renewal normally associated with hematopoietic stem cells (HSCs) and up-regulate a subset of MYC target genes important in maintaining stem/progenitor cell balance. In lymphocytes, genomic occupancy by MYC-T58A was increased at all promoters compared with WT MYC, while genes differentially expressed in a T58A-dependent manner were significantly more proximal to MYC-bound enhancers. MYC-T58A lymphocyte progenitors exhibited metabolic alterations and decreased activation of inflammatory and apoptotic pathways. Our data demonstrate that a single point mutation stabilizing MYC is sufficient to skew target gene expression, producing a profound gain of function in multipotential hematopoietic progenitors associated with self-renewal and initiation of lymphomas and leukemias.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"130 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140534443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fotini M Kouri, Lisa A Hurley, Weston L Daniel, Emily S Day, Youjia Hua, Liangliang Hao, Chian-Yu Peng, Timothy J Merkel, Markus A Queisser, Carissa Ritner, Hailei Zhang, C David James, Jacob I Sznajder, Lynda Chin, David A Giljohann, John A Kessler, Marcus E Peter, Chad A Mirkin, Alexander H Stegh
{"title":"Corrigendum: miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma.","authors":"Fotini M Kouri, Lisa A Hurley, Weston L Daniel, Emily S Day, Youjia Hua, Liangliang Hao, Chian-Yu Peng, Timothy J Merkel, Markus A Queisser, Carissa Ritner, Hailei Zhang, C David James, Jacob I Sznajder, Lynda Chin, David A Giljohann, John A Kessler, Marcus E Peter, Chad A Mirkin, Alexander H Stegh","doi":"10.1101/gad.351832.124","DOIUrl":"10.1101/gad.351832.124","url":null,"abstract":"","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"38 7-8","pages":"355"},"PeriodicalIF":10.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin B Steinfeld, Ondrej Beláň, Youngho Kwon, Tsuyoshi Terakawa, Amr Al-Zain, Michael J Smith, J Brooks Crickard, Zhi Qi, Weixing Zhao, Rodney Rothstein, Lorraine S Symington, Patrick Sung, Simon J Boulton, Eric C Greene
{"title":"Corrigendum: Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination.","authors":"Justin B Steinfeld, Ondrej Beláň, Youngho Kwon, Tsuyoshi Terakawa, Amr Al-Zain, Michael J Smith, J Brooks Crickard, Zhi Qi, Weixing Zhao, Rodney Rothstein, Lorraine S Symington, Patrick Sung, Simon J Boulton, Eric C Greene","doi":"10.1101/gad.351813.124","DOIUrl":"10.1101/gad.351813.124","url":null,"abstract":"","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"38 7-8","pages":"354"},"PeriodicalIF":10.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metabolic reprogramming of stem cells is a targetable pathway to control regeneration. Activation of stem cells results in down-regulation of oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) and turns on glycolysis to provide fuel for proliferation and specific signaling events. How cell type-specific events are regulated is unknown. In this issue of Genes & Development Ciuffoli and colleagues (pp. 151-167) use metabolomic, gene inactivation, and functional approaches to show that phosphoserine aminotransferase (Psat1), an enzyme in serine biosynthesis, is activated in muscle stem cells and contributes to cell expansion and skeletal muscle regeneration via the production of α-ketoglutarate and glutamine.
{"title":"A serine metabolic enzyme is flexing its muscle to help repair skeletal muscle.","authors":"Benjámin R Baráth, Laszlo Nagy","doi":"10.1101/gad.351666.124","DOIUrl":"10.1101/gad.351666.124","url":null,"abstract":"<p><p>Metabolic reprogramming of stem cells is a targetable pathway to control regeneration. Activation of stem cells results in down-regulation of oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) and turns on glycolysis to provide fuel for proliferation and specific signaling events. How cell type-specific events are regulated is unknown. In this issue of <i>Genes & Development</i> Ciuffoli and colleagues (pp. 151-167) use metabolomic, gene inactivation, and functional approaches to show that phosphoserine aminotransferase (Psat1), an enzyme in serine biosynthesis, is activated in muscle stem cells and contributes to cell expansion and skeletal muscle regeneration via the production of α-ketoglutarate and glutamine.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"95-97"},"PeriodicalIF":7.5,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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