Evidence map›Paper›PMID 36270248›Full record

ArticleMolecular cell2022

Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential.

Yuval Malka, Ferhat Alkan, Shinyeong Ju, Pierre-Rene Körner, Abhijeet Pataskar, Eldad Shulman, Fabricio Loayza-Puch, Julien Champagne, Casper Wenzel, William James Faller and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  5. Ins and outs of IRES elements: function and significance.Biochemical Society transactions · 2025
    Review
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  16. Exploring the uncharted landscape of truncated mRNAs.Nature reviews. Molecular cell biology · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 3 countries.

Yuval MalkaDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands. Electronic address: yuvalmalka79@gmail.com.
Ferhat AlkanDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
Shinyeong JuChemical & Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
Pierre-Rene KörnerDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
Abhijeet PataskarDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
Eldad ShulmanDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Fabricio Loayza-PuchDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
Julien ChampagneDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
Casper WenzelDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
William James FallerDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands.
Ran ElkonDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Cheolju LeeChemical & Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea.
Reuven AgamiDivision of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands; Erasmus MC, Rotterdam University, Rotterdam, the Netherlands. Electronic address: r.agami@nki.nl.
The Netherlands Cancer Institute · NLTel Aviv University · ILBio-Medical Science (South Korea) · KRErasmus MC · NLKorea Institute of Science and Technology · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates mRNA isoforms that expand the diversity and complexity of the transcriptome. Here, we uncovered thousands of previously undescribed 5' uncapped and polyadenylated transcripts (5' UPTs). We show that these transcripts resist exonucleases due to a highly structured RNA and N6-methyladenosine modification at their 5' termini. 5' UPTs appear downstream of APA sites within their host genes and are induced upon APA activation. Strong enrichment in polysomal RNA fractions indicates 5' UPT translational potential. Indeed, APA promotes downstream translation initiation, non-canonical protein output, and consistent changes to peptide presentation at the cell surface. Lastly, we demonstrate the biological importance of 5' UPTs using Bcl2, a prominent anti-apoptotic gene whose entire coding sequence is a 5' UPT generated from 5' UTR-embedded APA sites. Thus, APA is not only accountable for terminating transcripts, but also for generating downstream uncapped RNAs with translation potential and biological impact.

Indexed as

PolyadenylationRNA Isoforms3' Untranslated Regions5' Untranslated RegionsExonucleasesProto-Oncogene Proteins c-bcl-23' Untranslated Regions5' Untranslated RegionsExonucleasesProto-Oncogene Proteins c-bcl-2RNA Isoformsalternative cleavage and polyadenylationBcl2CAP-independent translationHidden Markov Modelimmunopeptidomemammalian transcriptomeN6-methyladenosineN-terminal mass spectrometryRNA structureuncapped RNA

Identifiers

PMID36270248
PMCPMC9636002
OpenAlexW4306885091

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.