Evidence map›Paper›PMID 42675053›Full record

ArticleNature communications2026

Unbiased screen of human transcriptome reveals an unexpected role of 3'UTRs in translation initiation.

Yun Yang, Xiaojuan Fan, Yanwen Ye, Zhenzhen Zhang, Chuyun Chen, Sebastian E J Ludwig, Sirui Zhang, Qianyun Lu, Cindy L Will, Henning Urlaub and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Yun Yang *Bio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China. yangyun@circodebio.com.
Xiaojuan Fan *Bio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Yanwen Ye *Bio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Zhenzhen Zhang *Department of Systems Biology, Innovative Center of RNA Medicine, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
Chuyun ChenBio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.ORCID 0000-0003-0550-9458
Sebastian E J LudwigEmeritus Group Cellular Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, Göttingen, Germany.
Sirui ZhangBio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Qianyun LuBio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Cindy L WillEmeritus Group Cellular Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, Göttingen, Germany.
Henning UrlaubBioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, Göttingen, Germany.
Jing SunBio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Reinhard LührmannEmeritus Group Cellular Biochemistry, Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, Göttingen, Germany.ORCID 0000-0003-3253-7518
Zefeng WangBio-med Big Data Center, CAS Key Laboratory of Computational Biology, University of Chinese Academy of Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China. wangzf@sustech.edu.cn.ORCID 0000-0002-6605-3637

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32530065
6 · The paper itself

Abstract

Although most eukaryotic mRNAs require a 5'-cap for translation initiation, some can also be translated through a poorly studied cap-independent pathway. Here we develop a circRNA-based system and unbiasedly identify more than 10,000 sequences in the human transcriptome that contain Cap-independent Translation Initiators (CiTIs). Surprisingly, most of the identified CiTIs are located in 3'UTRs, which mainly promote translation initiation in mRNAs bearing highly structured 5'UTR. Mechanistically, CiTI recruits several translation initiation factors including eIF3 and DHX29, which in turn unwind 5'UTR structures and facilitate ribosome scanning. Functionally, we show that the translation of HIF1A mRNA, an endogenous DHX29 target, is antagonistically regulated by its 5'UTR structure and a new 3'-CiTI in response to hypoxia. Consistently, deletion of 3'-CiTI suppresses cell growth in hypoxia and tumor progression in vivo. Collectively, our study uncovers a new regulatory mode for translation where the 3'UTR actively participate in the translation initiation.

Indexed as

3' Untranslated RegionsPeptide Chain Initiation, TranslationalTranscriptome5' Untranslated RegionsAnimalsCell HypoxiaDEAD-box RNA HelicasesEukaryotic Initiation Factor-3HEK293 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitMiceRibosomesRNA, Messenger3' Untranslated Regions5' Untranslated RegionsDEAD-box RNA HelicasesEukaryotic Initiation Factor-3HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitRNA, Messenger

Identifiers

PMID42675053
PMCPMC13530117

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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.