Imperial College London
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ProfessorBorisLenhard

Faculty of Medicine, Institute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 7594 0911b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

6.12CLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jobbins:2022:nar/gkac165,
author = {Jobbins, AM and Haberman, N and Artigas, N and Amourda, C and Paterson, HAB and Yu, S and Blackford, SJ and Montoya, A and Dore, M and Wang, Y-F and Sardini, A and Cebola, I and Zuber, J and Rashid, ST and Lenhard, B and Vernia, S},
doi = {nar/gkac165},
journal = {Nucleic Acids Research},
pages = {3379--3393},
title = {Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease},
url = {http://dx.doi.org/10.1093/nar/gkac165},
volume = {50},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here, we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD). Moreover, we find that Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding is enriched adjacent to consensus polyadenylation motifs and its expression is significantly decreased in NAFLD, suggesting a role mediating pre-mRNA dysregulation in this condition. Consistently, inactivation of SRSF10 in mouse and human hepatocytes in vitro, and in mouse liver in vivo, was found to dysregulate polyadenylation of key metabolic genes such as peroxisome proliferator-activated receptor alpha (PPARA) and exacerbate diet-induced metabolic dysfunction. Collectively our work implicates dysregulated pre-mRNA polyadenylation in obesity-induced liver disease and uncovers a novel role for SRSF10 in this process.
AU  - Jobbins,AM
AU  - Haberman,N
AU  - Artigas,N
AU  - Amourda,C
AU  - Paterson,HAB
AU  - Yu,S
AU  - Blackford,SJ
AU  - Montoya,A
AU  - Dore,M
AU  - Wang,Y-F
AU  - Sardini,A
AU  - Cebola,I
AU  - Zuber,J
AU  - Rashid,ST
AU  - Lenhard,B
AU  - Vernia,S
DO  - nar/gkac165
EP  - 3393
PY  - 2022///
SN  - 0305-1048
SP  - 3379
TI  - Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkac165
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000776743800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/nar/article/50/6/3379/6549377
UR  - http://hdl.handle.net/10044/1/100822
VL  - 50
ER  -
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