Integrator-Dependent and Allosteric/Intrinsic Mechanisms Ensure Efficient Termination of snRNA Transcription
Autor: | Laura Francis, Lee Davidson, Steven West, Joshua D. Eaton |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Integrator complex RNA polymerase II General Biochemistry Genetics and Molecular Biology RNA polymerase III allosteric 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Transcription (biology) snRNA RNA polymerase RNA Small Nuclear Report INTS11 Humans exosome cleavage polyadenylation XRN2 transcription termination biology Chemistry Integrator Cell biology 030104 developmental biology Transcription Termination Genetic SnRNA transcription biology.protein RNA Polymerase II Exoribonuclease activity 030217 neurology & neurosurgery Small nuclear RNA |
Zdroj: | Cell Reports |
ISSN: | 2211-1247 |
Popis: | Summary Many RNA polymerases terminate transcription using allosteric/intrinsic mechanisms, whereby protein alterations or nucleotide sequences promote their release from DNA. RNA polymerase II (Pol II) is somewhat different based on its behavior at protein-coding genes where termination additionally requires endoribonucleolytic cleavage and subsequent 5′→3′ exoribonuclease activity. The Pol-II-transcribed small nuclear RNAs (snRNAs) also undergo endoribonucleolytic cleavage by the Integrator complex, which promotes their transcriptional termination. Here, we confirm the involvement of Integrator but show that Integrator-independent processes can terminate snRNA transcription both in its absence and naturally. This is often associated with exosome degradation of snRNA precursors that long-read sequencing analysis reveals as frequently terminating at T-runs located downstream of some snRNAs. This finding suggests a unifying vulnerability of RNA polymerases to such sequences given their well-known roles in terminating Pol III and bacterial RNA polymerase. Graphical Abstract Highlights • Integrator-dependent and -independent mechanisms terminate snRNA transcription • Integrator-independent termination is allosteric/intrinsic in nature • Sites of allosteric/intrinsic termination often coincide with T-runs • Some Pol II termination may share features with Pol III/prokaryotic mechanisms Davidson et al. show that termination of RNA polymerase II transcription at human snRNA genes can occur by Integrator-dependent and -independent pathways. The latter uses an allosteric/intrinsic mechanism most efficiently detected where T-runs are present in the non-template strand. This is reminiscent of the way many other RNA polymerases terminate. |
Databáze: | OpenAIRE |
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