Int. J. Mol. Sci. 2014, 15(2), 2946-2958; doi:10.3390/ijms15022946
Article

HuR and TIA1/TIAL1 Are Involved in Regulation of Alternative Splicing of SIRT1 Pre-mRNA

1email, 1email, 1email, 1email, 1email, 1email, 1,* email and 2,* email
Received: 19 November 2013; in revised form: 19 January 2014 / Accepted: 10 February 2014 / Published: 20 February 2014
(This article belongs to the Special Issue Pre-mRNA Splicing)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: SIRT1 is a pleiotropic protein that plays critical and multifunctional roles in metabolism, senescence, longevity, stress-responses, and cancer, and has become an important therapeutic target across a range of diseases. Recent research demonstrated that SIRT1 pre-mRNA undergoes alternative splicing to produce different isoforms, such as SIRT1 full-length and SIRT1-∆Exon8 variants. Previous studies revealed these SIRT1 mRNA splice variants convey different characteristics and functions to the protein, which may in turn explain the multifunctional roles of SIRT1. However, the mechanisms underlying the regulation of SIRT1 alternative splicing remain to be elucidated. Our objective is to search for new pathways that regulate of SIRT1 alternative splicing. Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances: HuR increased SIRT1-∆Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-∆Exon8 mRNA levels. This study provides novel insight into how the alternative splicing of SIRT1 pre-mRNA is regulated, which has fundamental implications for understanding the critical and multifunctional roles of SIRT1.
Keywords: SIRT1; alternative splicing; SIRT1-∆Exon8; Hu antigen R; T-cell-restricted intracellular antigen 1; TIA1-like 1
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MDPI and ACS Style

Zhao, W.; Zhao, J.; Hou, M.; Wang, Y.; Zhang, Y.; Zhao, X.; Zhang, C.; Guo, D. HuR and TIA1/TIAL1 Are Involved in Regulation of Alternative Splicing of SIRT1 Pre-mRNA. Int. J. Mol. Sci. 2014, 15, 2946-2958.

AMA Style

Zhao W, Zhao J, Hou M, Wang Y, Zhang Y, Zhao X, Zhang C, Guo D. HuR and TIA1/TIAL1 Are Involved in Regulation of Alternative Splicing of SIRT1 Pre-mRNA. International Journal of Molecular Sciences. 2014; 15(2):2946-2958.

Chicago/Turabian Style

Zhao, Wenhui; Zhao, Jinfeng; Hou, Miaomiao; Wang, Yue; Zhang, Yang; Zhao, Xin; Zhang, Ce; Guo, Dawei. 2014. "HuR and TIA1/TIAL1 Are Involved in Regulation of Alternative Splicing of SIRT1 Pre-mRNA." Int. J. Mol. Sci. 15, no. 2: 2946-2958.


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