Transcription-Austin最新文献

Transposable elements (TEs) are repetitive DNA sequences with the ability to replicate across genomes and generate mutations with major transcriptional effects. Epigenetic silencing mechanisms that target TEs to limit their activity, including DNA methylation, add to the range of gene expression variants generated by TEs. Here, using the iconic gene flowering locus C (FLC) as a case study I discuss the multiple ways by which TEs can affect the expression of genes and contribute to the adaptation of plants to changing environments.

Plants have a high level of developmental plasticity that allows them to respond and adapt to changes in the environment. Among the environmental cues, light controls almost every aspect of A. thaliana's life cycle, including seed maturation, seed germination, seedling de-etiolation and flowering time. Light signals induce massive reprogramming of gene expression, producing changes in RNA polymerase II transcription, alternative splicing, and chromatin state. Since splicing reactions occur mainly while transcription takes place, the regulation of RNAPII transcription has repercussions in the splicing outcomes. This cotranscriptional nature allows a functional coupling between transcription and splicing, in which properties of the splicing reactions are affected by the transcriptional process. Chromatin landscapes influence both transcription and splicing. In this review, we highlight, summarize and discuss recent progress in the field to gain a comprehensive insight on the cross-regulation between chromatin state, RNAPII transcription and splicing decisions in plants, with a special focus on light-triggered responses. We also introduce several examples of transcription and splicing factors that could be acting as coupling factors in plants. Unravelling how these connected regulatory networks operate, can help in the design of better crops with higher productivity and tolerance.

Multisubunit RNA polymerase (Pol) complexes are the core machinery for gene expression in eukaryotes. The enzymes Pol I, Pol II and Pol III transcribe distinct subsets of nuclear genes. This family of nuclear RNA polymerases expanded in terrestrial plants by the duplication of Pol II subunit genes. Two Pol II-related enzymes, Pol IV and Pol V, are highly specialized in the production of regulatory, non-coding RNAs. Pol IV and Pol V are the central players of RNA-directed DNA methylation (RdDM), an RNA interference pathway that represses transposable elements (TEs) and selected genes. Genetic and biochemical analyses of Pol IV/V subunits are now revealing how these enzymes evolved from ancestral Pol II to sustain non-coding RNA biogenesis in silent chromatin. Intriguingly, Pol IV-RdDM regulates genes that influence flowering time, reproductive development, stress responses and plant-pathogen interactions. Pol IV target genes vary among closely related taxa, indicating that these regulatory circuits are often species-specific. Data from crops like maize, rice, tomato and Brassicarapa suggest that dynamic repositioning of TEs, accompanied by Pol IV targeting to TE-proximal genes, leads to the reprogramming of plant gene expression over short evolutionary timescales.

Plants have adapted to tolerate and survive constantly changing environmental conditions by reprogramming gene expression in response to stress or to drive developmental transitions. Among the many signals that plants perceive, light and temperature are of particular interest due to their intensely fluctuating nature which is combined with a long-term seasonal trend. Whereas specific receptors are key in the light-sensing mechanism, the identity of plant thermosensors for high and low temperatures remains far from fully addressed. This review aims at discussing common as well as divergent characteristics of gene expression regulation in plants, controlled by light and temperature. Light and temperature signaling control the abundance of specific transcription factors, as well as the dynamics of co-transcriptional processes such as RNA polymerase elongation rate and alternative splicing patterns. Additionally, sensing both types of cues modulates gene expression by altering the chromatin landscape and through the induction of long non-coding RNAs (lncRNAs). However, while light sensing is channeled through dedicated receptors, temperature can broadly affect chemical reactions inside plant cells. Thus, direct thermal modifications of the transcriptional machinery add another level of complexity to plant transcriptional regulation. Besides the rapid transcriptome changes that follow perception of environmental signals, plant developmental transitions and acquisition of stress tolerance depend on long-term maintenance of transcriptional states (active or silenced genes). Thus, the rapid transcriptional response to the signal (Phase I) can be distinguished from the long-term memory of the acquired transcriptional state (Phase II - remembering the signal). In this review we discuss recent advances in light and temperature signal perception, integration and memory in Arabidopsis thaliana, focusing on transcriptional regulation and highlighting the contrasting and unique features of each type of cue in the process.

The production of mRNA is a dynamic process that is highly regulated by reversible post-translational modifications of the C-terminal domain (CTD) of RNA polymerase II. The CTD is a highly repetitive domain consisting mostly of the consensus heptad sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Phosphorylation of serine residues within this repeat sequence is well studied, but modifications of all residues have been described. Here, we focus on integrating newly identified and lesser-studied CTD post-translational modifications into the existing framework. We also review the growing body of work demonstrating crosstalk between different CTD modifications and the functional consequences of such crosstalk on the dynamics of transcriptional regulation.

Recent biophysical studies of mycobacterial transcription have shed new light on this fundamental process in a group of bacteria that includes deadly pathogens such as Mycobacterium tuberculosis (Mtb), Mycobacterium abscessus (Mab), Mycobacterium leprae (Mlp), as well as the nonpathogenic Mycobacterium smegmatis (Msm). Most of the research has focused on Mtb, the causative agent of tuberculosis (TB), which remains one of the top ten causes of death globally. The enzyme RNA polymerase (RNAP) is responsible for all bacterial transcription and is a target for one of the crucial antibiotics used for TB treatment, rifampicin (Rif). Here, we summarize recent biophysical studies of mycobacterial RNAP that have advanced our understanding of the basic process of transcription, have revealed novel paradigms for regulation, and thus have provided critical information required for developing new antibiotics against this deadly disease.

The majority of eukaryotic messenger RNA precursors (pre-mRNAs) undergo cleavage and polyadenylation at their 3' end. This canonical 3'-end processing depends on sequence elements in the pre-mRNA as well as a mega-dalton protein machinery. The cleavage site in mammalian pre-mRNAs is located between an upstream poly(A) signal, most frequently an AAUAAA hexamer, and a GU-rich downstream sequence element. This review will summarize recent advances from the studies on this canonical 3'-end processing machinery. They have revealed the molecular mechanism for the recognition of the poly(A) signal and provided the first glimpse into the overall architecture of the machinery. The studies also show that the machinery is highly dynamic conformationally, and extensive re-arrangements are necessary for its activation. Inhibitors targeting the active site of the CPSF73 nuclease of this machinery have anti-cancer, anti-inflammatory and anti-protozoal effects, indicating that CPSF73 and pre-mRNA 3'-end processing in general are attractive targets for drug discovery.

Abbreviations: APA: alternative polyadenylation; β-CASP: metallo-β-lactamase-associated CPSF Artemis SNM1/PSO2; CTD: C-terminal domain; CF: cleavage factor; CPF: cleavage and polyadenylation factor; CPSF: cleavage and polyadenylation specificity factor; CstF: cleavage stimulation factor; DSE: downstream element; HAT: half a TPR; HCC: histone pre-mRNA cleavage complex; mCF: mammalian cleavage factor; mPSF: mammalian polyadenylation specificity factor; mRNA: messenger RNA; nt: nucleotide; NTD: N-terminal domain; PAP: polyadenylate polymerase; PAS: polyadenylation signal; PIM: mPSF interaction motif; Poly(A): polyadenylation, polyadenylate; Pol II: RNA polymerase II; pre-mRNA: messenger RNA precursor; RRM: RNA recognition module, RNA recognition motif; snRNP: small nuclear ribonucleoprotein; TPR: tetratricopeptide repeat; UTR: untranslated region; ZF: zinc finger.

Nascent transcription assays, such as global run-on sequencing (GRO-seq) and precision run-on sequencing (PRO-seq), have uncovered a myriad of unstable RNAs being actively produced from numerous sites genome-wide. These transcripts provide a more complete and immediate picture of the impact of regulatory events. Transcription factors recruit RNA polymerase II, effectively initiating the process of transcription; repressors inhibit polymerase recruitment. Efficiency of recruitment is dictated by sequence elements in and around the RNA polymerase loading zone. A combination of sequence elements and RNA binding proteins subsequently influence the ultimate stability of the resulting transcript. Some of these transcripts are capable of providing feedback on the process, influencing subsequent transcription. By monitoring RNA polymerase activity, nascent assays provide insights into every step of the regulated process of transcription.

Since the discovery that enhancers can support transcription, the roles of enhancer RNAs have remained largely elusive. We identified that enhancer RNAs interact with and augment bromodomain engagement with acetylated chromatin. Here, we discuss our recent findings and the potential mechanisms underlying the regulation and functions of enhancer RNA-bromodomain associations.