Evidence map›Paper›PMID 41805127›Full record

ArticleNucleic acids research2026

Alternative polyadenylation links RNA processing to iron metabolism in human erythropoiesis.

Shan Yu, Xianyan Zeng, Jing Chen, Zheqi Lou, Tinghui Jiang, Yangxin Ou, Peizhen Du, Jiyao Rao, Xinyan Dai, Ming Gong and 5 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Shan YuCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Xianyan ZengCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Jing ChenDepartment of Rheumatology, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing 404100, China.
Zheqi LouCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Tinghui JiangCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Yangxin OuCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Peizhen DuCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Jiyao RaoCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Xinyan DaiCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Ming GongCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Jing XuDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
Ping YiDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.ORCID 0000-0001-9025-612X
Fang WangState Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Xiaoshuang WangState Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Yong ZhuCollege of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.ORCID 0000-0002-4645-9883

Funding

National Key Research and Development Program of China 2024YFA1803504National Natural Science Foundation of China 82070111National Natural Science Foundation of China 92368108
6 · The paper itself

Abstract

Erythropoiesis requires precise coordination of transcriptional and co-/post-transcriptional programs, yet the role of alternative polyadenylation (APA) in this process remains poorly understood. Here, we profiled the genome-wide dynamic APA landscape during erythropoiesis using single-cell RNA sequencing (scRNA-seq). Through clustering and functional enrichment analysis, seven distinct APA dynamic patterns were identified, with genes showing stage-specific APA changes enriched in erythroid lineage differentiation, heme synthesis, and iron metabolism. Combining motif analysis near polyadenylation sites (PASs) and APA regulators expression profiling, we observed that cleavage and polyadenylation specificity factor 6 (CPSF6), a critical APA regulator, exhibited significant variation. Functional assays demonstrated that CPSF6 facilitates erythropoiesis, as its depletion impaired heme synthesis and intracellular iron deficiency. Mechanistically, CPSF6 depletion shortened the 3'UTR length of iron metabolism regulators (FAM210B, IREB2, TFRC), which was accompanied by reduced expression of these genes. Clinically, CPSF6 and these APA-regulated iron metabolism-related genes were aberrantly upregulated in polycythemia vera (PV) patients, correlating with erythroid hyperproliferation. Collectively, our findings support a CPSF6-APA-iron homeostasis axis as an important co-/post- transcriptional regulatory mechanism in erythropoiesis, and implicate its dysregulation in the pathogenesis of PV, offering novel molecular targets for therapeutic intervention in myeloproliferative neoplasms.

Indexed as

Cleavage And Polyadenylation Specificity FactorErythropoiesisIronPolyadenylationRNA Processing, Post-Transcriptional3' Untranslated RegionsHemeHumansPolycythemia Vera3' Untranslated RegionsCleavage And Polyadenylation Specificity FactorHemeIron

Identifiers

PMID41805127
PMCPMC12972907

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.