Evidence map›Paper›PMID 29432121›Full record

ArticleGenes & development2018

Xrn2 accelerates termination by RNA polymerase II, which is underpinned by CPSF73 activity.

Joshua D Eaton, Lee Davidson, David L V Bauer, Toyoaki Natsume, Masato T Kanemaki, Steven West

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 144 citations in OpenAlex.

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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Joshua D Eaton *The Living Systems Institute, University of Exeter, Exeter EX4 4QD, United Kingdom.
Lee Davidson *The Living Systems Institute, University of Exeter, Exeter EX4 4QD, United Kingdom.
David L V BauerSir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Toyoaki NatsumeDivision of Molecular Cell Engineering, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan.
Masato T KanemakiDivision of Molecular Cell Engineering, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan.
Steven WestThe Living Systems Institute, University of Exeter, Exeter EX4 4QD, United Kingdom.
University of Exeter · GBNational Institute of Genetics · JPThe Graduate University for Advanced Studies, SOKENDAI · JPUniversity of Oxford · GB

Funding

Medical Research Council MR/K000241/1Wellcome TrustWellcome Trust WT107791/Z/15/Z
6 · The paper itself

Abstract

Termination is a ubiquitous phase in every transcription cycle but is incompletely understood and a subject of debate. We used gene editing as a new approach to address its mechanism through engineered conditional depletion of the 5' → 3' exonuclease Xrn2 or the polyadenylation signal (PAS) endonuclease CPSF73 (cleavage and polyadenylation specificity factor 73). The ability to rapidly control Xrn2 reveals a clear and general role for it in cotranscriptional degradation of 3' flanking region RNA and transcriptional termination. This defect is characterized genome-wide at high resolution using mammalian native elongating transcript sequencing (mNET-seq). An Xrn2 effect on termination requires prior RNA cleavage, and we provide evidence for this by showing that catalytically inactive CPSF73 cannot restore termination to cells lacking functional CPSF73. Notably, Xrn2 plays no significant role in either Histone or small nuclear RNA (snRNA) gene termination even though both RNA classes undergo 3' end cleavage. In sum, efficient termination on most protein-coding genes involves CPSF73-mediated RNA cleavage and cotranscriptional degradation of polymerase-associated RNA by Xrn2. However, as CPSF73 loss caused more extensive readthrough transcription than Xrn2 elimination, it likely plays a more underpinning role in termination.

Indexed as

Transcription Termination, Genetic3' Untranslated RegionsCell LineCleavage And Polyadenylation Specificity FactorExoribonucleasesHigh-Throughput Nucleotide SequencingHistonesHumansIndoleacetic AcidsMutationRNA Polymerase IIRNA, Small NuclearSequence Analysis, RNA3' Untranslated RegionsCleavage And Polyadenylation Specificity FactorExoribonucleasesHistonesIndoleacetic AcidsRNA Polymerase IIRNA, Small NuclearXRN2 protein, humanallostericCPSF73RNA polymerase IItorpedotranscriptional terminationXrn2

Identifiers

PMID29432121
PMCPMC5830926
OpenAlexW2785666349

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.