FEBS Letters最新文献

Enhancers are non-coding cis-regulatory elements crucial for transcriptional regulation. Mutations in enhancers can disrupt gene regulation, leading to disease phenotypes. Identifying enhancers and their tissue-specific activity is challenging due to their lack of stereotyped sequences. This study presents a sequence-based computational model that uses combinatorial transcription factor (TF) genomic occupancy to predict tissue-specific enhancers. Trained on diverse datasets, including ENCODE and Vista enhancer browser data, the model predicted 25 000 forebrain-specific cis-regulatory modules (CRMs) in the human genome. Validation using biochemical features, disease-associated SNPs, and in vivo zebrafish analysis confirmed its effectiveness. This model aids in predicting enhancers lacking well-characterized chromatin features, complementing experimental approaches in tissue-specific enhancer discovery.

Science communication is an important skill. It is easier for nonacademic audiences to remember stories that resonate with their imagination rather than facts and figures. To help early-career researchers develop their skills, the EU-LIFE Science Communications Working Group (SCWG) developed a training course based on the experience from previous workshops held at a research institute in Denmark. The stories crafted in the workshops proved impactful, with some integrated into broader campaigns and featured in science magazines. The initiative holds potential for transformative change, helping researchers promote their findings and increasing awareness of emerging research topics among the public. Recently, the initiative has been customized for a summer school aimed at medical doctors pursuing a PhD, marking a step forward in the SCWG's mission to equip researchers with essential communication skills.

PIWI-interacting RNAs (piRNAs) were discovered in the early 2000s and became known for their role in protecting the germline genome against mobile genetic elements. Successively, piRNAs were also detected in the somatic cells of gonads in multiple animal species. In recent years, piRNAs have been reported in non-gonadal tissues in various arthropods, contrary to the initial assumptions of piRNAs being exclusive to gonads. Here, we performed an extensive literature review, which revealed that reports on non-gonadal somatic piRNA expression are not limited to a few specific species. Instead, when multiple studies are considered collectively, it appears to be a widespread phenomenon across arthropods. Furthermore, we systematically analyzed 168 publicly available small RNA-seq datasets from diverse tissues in 17 species, which further supported the bibliographic reports that piRNAs are expressed across tissues and species in Arthropoda.

RETRACTION: J. J. Wu, X. D. Zhang, S. Gillespie, and P. Hersey, “Selection for TRAIL Resistance Results in Melanoma Cells with High Proliferative Potential,” FEBS Letters 579, no. 9 (2005): 1940–1944, https://doi.org/10.1016/j.febslet.2005.02.041.

The above article, published online on February 25, 2005, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Michael Brunner; FEBS Press; and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate duplications of image sections within the article (Fig. 2A, 3A-C, 4A-B) depicting different experimental conditions. The authors were unable to provide a satisfactory explanation and due to the elapsed time the raw data was not available. Given the extent of the identified issues, the editors have lost confidence in the data presented and the article's conclusions can no longer be considered reliable.

Transcription of actively expressed genes is dampened for kilobases around DNA lesions via chromatin modifications. This is believed to favour repair and prevent genome instability. Nonetheless, mounting evidence suggests that transcription may be induced by DNA breakage, resulting in the local de novo synthesis of non-coding RNAs (ncRNAs). Such transcripts have been proposed to play important functions in both DNA damage signalling and repair. Here, we review the recently identified mechanistic details of transcriptional silencing at damaged chromatin, highlighting how post-translational histone modifications can also be modulated by the local synthesis of DNA damage-induced ncRNAs. Finally, we envision that these entangled transcriptional events at DNA breakages can be targeted to modulate DNA repair, with potential implications for locus-specific therapeutic strategies.

As the most compact variant in the Cas13 family, CRISPR-Cas13X holds considerable promise for gene therapy applications. The development of high-fidelity Cas13X (hfCas13X) mutants has enhanced the safety profile for in vivo applications. However, a notable reduction in on-target cleavage efficiency accompanies the diminished collateral cleavage activity in hfCas13X. In this study, we obtained two engineered crRNA mutants that notably enhance the on-target cleavage efficiency of hfCas13X. Furthermore, we have identified a novel crRNA structure that consistently augments the on-target cleavage efficiency of hfCas13X across various cellular environments, without significant enhancement of its collateral activity. These findings collectively enrich the gene-editing toolkit, presenting a more effective hfCas13X system for future research and application.

Cytokinesis leads to the distribution of segregated chromosomes, membrane, and cytoplasmic material in the two daughter cells, and ultimately concludes with abscission, their physical separation. In this Graphical Review, we outline the key events that lead to abscission and discuss mechanisms of delayed abscisison.

Heart failure (HF) is highly prevalent. Mechanisms underlying HF remain incompletely understood. Splicing factors (SF), which control pre-mRNA alternative splicing, regulate cardiac structure and function. This study investigated regulation of the splicing factor heterogeneous nuclear ribonucleoprotein-L (hnRNPL) in the failing heart. hnRNPL protein increased in left ventricular tissue from mice with transaortic constriction-induced HF and from HF patients. In left ventricular tissue, hnRNPL was detected predominantly in nuclei. Knockdown of the hnRNPL homolog Smooth in Drosophila induced cardiomyopathy. Computational analysis of predicted mouse and human hnRNPL binding sites suggested hnRNPL-mediated alternative splicing of tropomyosin, which was confirmed in C2C12 myoblasts. These findings identify hnRNPL as a sensor of cardiac dysfunction and suggest that disturbances of hnRNPL affect alternative splicing in HF.

In inner ear hair cells, the stereocilia are inserted into a dense F-actin-enriched meshwork named the cuticular plate, which provides support to the stereocilia. Enah/Vasp-like (EVL) was shown to localize at the cuticular plate, and evl knockdown leads to disrupted cuticular plate and disorganized stereocilia in Xenopus hair cells. In the present work, we show that Evl transcripts are specifically expressed in mouse hair cells, and EVL is localized to the cuticular plate. However, the cuticular plate and stereocilia are unaffected by Evl knockout, and auditory function is largely normal in Evl knockout mice. In conclusion, our present data suggest that EVL is not essential for cuticular plate and stereocilia development in mouse auditory hair cells.

RETRACTION: R. Bakalova, H. Ohba, Z. Zhelev, T. Kubo, M. Fujii, M. Ishikawa, Y. Shinohara, and Y. Baba, ‘Antisense inhibition of Bcr-Abl/c-Abl synthesis promotes telomerase activity and upregulates tankyrase in human leukemia cells,' FEBS Letters 564, no. 1–2 (2004): 73–84, https://doi.org/10.1016/S0014-5793(04)00318-7.

The above article, published online on 9 April 2004 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Michael Brunner; FEBS Press; the National Institute of Advanced Industrial Science and Technology (AIST); and John Wiley and Sons Ltd.

Following publication, concerns were raised by a third-party regarding several figures in the article. The subsequent institutional investigation conducted by the AIST revealed:

Therefore, the conclusions of the paper are substantially compromised and the institute has recommended the paper to be retracted. The editors of the journal agree with the retraction based on the institutional investigation.