Evidence map›Paper›PMID 33440169›Full record

ArticleMolecular cell2021

Co-transcriptional splicing regulates 3' end cleavage during mammalian erythropoiesis.

Kirsten A Reimer, Claudia A Mimoso, Karen Adelman, Karla M Neugebauer

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 1 pooled it
13.0field-weighted citation impact, top 1% of its field
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

117 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.

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  19. Extensive splicing deficiency in a degenerating mating-type chromosome.bioRxiv : the preprint server for biology · 2025
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57 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

4 authors at 2 institutions in 1 country.

Kirsten A ReimerDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Claudia A MimosoDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Karen AdelmanDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Karla M NeugebauerDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. Electronic address: karla.neugebauer@yale.edu.
Harvard University · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Cooperative Hematology Specialized Core CenterU54DK106857 · NIDDK · YALE UNIVERSITY · PI JOHN HWA, Diane S Krause · 2015 to 2026
$9.7M
Cross-regulation between transcription and pre-mRNA splicingR01GM112766 · NIGMS · YALE UNIVERSITY · PI Karla M Neugebauer · 2015 to 2026
$5.3M
Analysis of transcription and splicing coordination during erythropoeisis using single molecule RNA-seqR21HL150642 · NHLBI · YALE UNIVERSITY · PI NEUGEBAUER, KARLA M, PILLAI, MANOJ M. · 2020 to 2021
$459k
Pacific Bioscience Sequel II sequencing system for the Yale Center for Genome Analysis (YCGA)S10OD028669 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2020 to 2020
$407k
NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R21 HL150642NIDDK NIH HHS U54 DK106857NIGMS NIH HHS R01 GM112766NIH HHS S10 OD028669
6 · The paper itself

Abstract

Pre-mRNA processing steps are tightly coordinated with transcription in many organisms. To determine how co-transcriptional splicing is integrated with transcription elongation and 3' end formation in mammalian cells, we performed long-read sequencing of individual nascent RNAs and precision run-on sequencing (PRO-seq) during mouse erythropoiesis. Splicing was not accompanied by transcriptional pausing and was detected when RNA polymerase II (Pol II) was within 75-300 nucleotides of 3' splice sites (3'SSs), often during transcription of the downstream exon. Interestingly, several hundred introns displayed abundant splicing intermediates, suggesting that splicing delays can take place between the two catalytic steps. Overall, splicing efficiencies were correlated among introns within the same transcript, and intron retention was associated with inefficient 3' end cleavage. Remarkably, a thalassemia patient-derived mutation introducing a cryptic 3'SS improved both splicing and 3' end cleavage of individual β-globin transcripts, demonstrating functional coupling between the two co-transcriptional processes as a determinant of productive gene output.

Indexed as

RNA SplicingTranscription Elongation, GeneticAnimalsBase Sequencebeta-Globinsbeta-ThalassemiaCell DifferentiationCell Line, TumorErythroid CellsErythropoiesisExonsHumansIntronsLeukocytesMiceMutationbeta-GlobinsRNA Polymerase IIRNA Splice Sitesco-transcriptional splicingerythropoiesisglobinlong-read sequencingnascent RNAPacBio

Identifiers

PMID33440169
PMCPMC8038867
OpenAlexW3121080183

What OpenQuestion holds

Textmetadata
LicenceTDM
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.