Evidence map›Paper›PMID 39187547›Full record

ArticleCell death & disease2024

KHSRP ameliorates acute liver failure by regulating pre-mRNA splicing through its interaction with SF3B1.

Mingxuan Li, Qian Fang, Pingping Xiao, Zhinang Yin, Guangbo Mei, Cheng Wang, Ying Xiang, Xuejun Zhao, Lihua Qu, Tian Xu and 6 more

Abstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

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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

16 authors.

Mingxuan Li *Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Qian Fang *Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.ORCID 0009-0004-1468-6549
Pingping Xiao *Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Zhinang Yin *Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Guangbo MeiHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Cheng WangHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Ying XiangDepartment of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Xuejun ZhaoHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Lihua QuHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.ORCID 0009-0008-2157-4659
Tian XuHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Jiaxi ZhangHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Kejun LiuHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Xiaoqing LiCenter for Stem Cell Research and Application, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Huifen DongHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.ORCID 0000-0003-2787-5694
Ruijing XiaoHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China. 00009774@whu.edu.cn.ORCID 0000-0002-5753-6557
Rui ZhouHubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430071, China. ruizhou@whu.edu.cn.ORCID 0000-0002-9927-5236

Funding

National Natural Science Foundation of China (National Science Foundation of China) No. 81971966National Natural Science Foundation of China (National Science Foundation of China) No. 82271795
6 · The paper itself

Abstract

Acute liver failure (ALF) is characterized by the rapidly progressive deterioration of hepatic function, which, without effective medical intervention, results in high mortality and morbidity. Here, using proteomic and transcriptomic analyses in murine ALF models, we found that the expression of multiple splicing factors was downregulated in ALF. Notably, we found that KH-type splicing regulatory protein (KHSRP) has a protective effect in ALF. Knockdown of KHSRP resulted in dramatic splicing defects, such as intron retention, and led to the exacerbation of liver injury in ALF. Moreover, we demonstrated that KHSRP directly interacts with splicing factor 3b subunit 1 (SF3B1) and enhances the binding of SF3B1 to the intronic branch sites, thereby promoting pre-mRNA splicing. Using splicing inhibitors, we found that Khsrp protects against ALF by regulating pre-mRNA splicing in vivo. Overall, our findings demonstrate that KHSRP is an important splicing activator and promotes the expression of genes associated with ALF progression by interacting with SF3B1; thus, KHSRP could be a possible target for therapeutic intervention in ALF.

Indexed as

Liver Failure, AcuteRNA-Binding ProteinsRNA PrecursorsRNA SplicingRNA Splicing FactorsAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLPhosphoproteinsProtein BindingTrans-ActivatorsKhsrp protein, mousePhosphoproteinsRNA-Binding ProteinsRNA PrecursorsRNA Splicing FactorsSF3B1 protein, humanSf3b1 protein, mouseTrans-Activators

Identifiers

PMID39187547
PMCPMC11347664

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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.