Transcription Termination: Variations on Common Themes

Porrúa, Odil; Boudvillain, Marc; Libri, Domenico

doi:10.1016/j.tig.2016.05.007

Cited by 100 publications

(132 citation statements)

References 108 publications

(160 reference statements)

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“…The resulting 3′‐end fragment of the pre‐mRNA is processed by the 5′‐3′ exonuclease XRN2. According to the “torpedo” termination model, XRN2 attacks the newly formed 5′‐end of the read‐through transcript, chases up and eventually destabilizes the elongating RNAP II, leading to transcriptional termination (Eaton & West, ; Porrua, Boudvillain, & Libri, ; Proudfoot, ; Richard & Manley, ). Previous studies have revealed that the p54nrb‐PSF complex, which binds to CTD, recruits XRN2 to the CstF complex of the CPA machinery on transcriptionally active loci, thus coupling transcription, CPA and termination (Emili et al, ; Kaneko, Rozenblatt‐Rosen, Meyerson, & Manley, ).…”

Section: Introductionmentioning

confidence: 99%

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

et al. 2019

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A multiprotein complex, THO/TREX, couples the transcription, 3′‐end formation and nuclear export of mRNAs. In this study, we report that crucial factors for mRNA processing, such as XRN2, DDX5/DDX17 and CstF64, are copurified with human THO (hTHO). Using chromatin immunoprecipitation, we found increased cross‐linking of XRN2 and CstF64 to the RNA polymerase II (RNAP II) pause site of the HSPA1A gene upon down‐regulation of THOC5, a metazoan‐specific component of hTHO. As observed in THOC5‐depleted cells, knockdown of XRN2 blocked HSP70 transcript release and increased the amount of CstF64 at the pause site. In addition, our data indicate that DDX5/DDX17 is also required for HSP70 transcript release. As the degradation of read‐through transcripts, but not cleavage at polyadenylation sites per se, was hindered upon THOC5 or DDX5/DDX17 down‐regulation, these factors appear to influence transcriptional termination. Interestingly, over‐expression of RNase H suppressed the accumulation of HSP70 transcripts in nuclear foci in THOC5‐ or DDX5/DDX17‐depleted cells. Thus, we propose a model in which hTHO, along with DDX5/DDX17, restricts the formation of R‐loops, thereby facilitating the XRN2‐mediated transcriptional termination and release of the mature transcript from the HSPA1A locus.

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Section: Introductionmentioning

confidence: 99%

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

et al. 2019

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“…Transcription termination determines the ends of transcriptional units by disassembling the transcription elongation complex (TEC), thereby releasing RNA polymerases and nascent transcripts from DNA templates (Porrua et al 2016;Proudfoot 2016). Failure in termination causes transcription readthrough, which yields wasteful and possibly harmful intergenic transcripts.…”

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confidence: 99%

Two distinct transcription termination modes dictated by promoters

2017

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Transcription termination determines the ends of transcriptional units and thereby ensures the integrity of the transcriptome and faithful gene regulation. Studies in yeast and human cells have identified the exoribonuclease XRN2 as a key termination factor for protein-coding genes. Here we performed a genome-wide investigation of RNA polymerase II (Pol II) transcription termination in XRN2-deficient Caenorhabditis elegans and observed two distinct modes of termination. Although a subset of genes requires XRN2, termination of other genes appears both independent of, and refractory to, XRN2. XRN2 independence is not merely a consequence of failure to recruit XRN2, since XRN2 is present on-and promotes Pol II accumulation near the polyadenylation sites of-both gene classes. Unexpectedly, promoters instruct the choice of termination mode, but XRN2-independent termination additionally requires a compatible region downstream from the 3 ′ end cleavage site. Hence, different termination mechanisms may work with different configurations of Pol II complexes dictated by promoters.

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“…However, to confirm this proposal, we must explain why many R ≥ 8S ≤ 8 IRs stretch over the gene ends. The Rho-independent transcription termination usually occurs several bp downstream from the terminators (Ray-Soni et al 2016; Porrua et al 2016). Thus, the IRs “must” always be located in the upstream of the gene ends, if they are used in transcription termination.…”

Section: Discussionmentioning

confidence: 99%

Requirement or exclusion of inverted repeat sequences with cruciform-forming potential in Escherichia coli revealed by genome-wide analyses

2018

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Inverted repeat (IR) sequences are DNA sequences that read the same from 5′ to 3′ in each strand. Some IRs can form cruciforms under the stress of negative supercoiling, and these IRs are widely found in genomes. However, their biological significance remains unclear. The aim of the current study is to explore this issue further. We constructed the first Escherichia coli genome-wide comprehensive map of IRs with cruciform-forming potential. Based on the map, we performed detailed and quantitative analyses. Here, we report that IRs with cruciform-forming potential are statistically enriched in the following five regions: the adjacent regions downstream of the stop codon-coding sites (referred to as the stop codons), on and around the positions corresponding to mRNA ends (referred to as the gene ends), ~ 20 to ~45 bp upstream of the start codon-coding sites (referred to as the start codons) within the 5′-UTR (untranslated region), ~ 25 to ~ 60 bp downstream of the start codons, and promoter regions. For the adjacent regions downstream of the stop codons and on and around the gene ends, most of the IRs with a repeat unit length of ≥ 8 bp and a spacer size of ≤ 8 bp were parts of the intrinsic terminators, regardless of the location, and presumably used for Rho-independent transcription termination. In contrast, fewer IRs were present in the small region preceding the start codons. In E. coli, IRs with cruciform-forming potential are actively placed or excluded in the regulatory regions for the initiation and termination of transcription and translation, indicating their deep involvement or influence in these processes.Electronic supplementary materialThe online version of this article (10.1007/s00294-018-0815-y) contains supplementary material, which is available to authorized users.

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Transcription Termination: Variations on Common Themes

Cited by 100 publications

References 108 publications

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

Two distinct transcription termination modes dictated by promoters

Requirement or exclusion of inverted repeat sequences with cruciform-forming potential in Escherichia coli revealed by genome-wide analyses

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