title: HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA.
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.
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. wenhui8088@gmail.com.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. jinfeng801229@gmail.com.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. houmiaomiaodeshijie@gmail.com.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. fairymoon0325@gmail.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. marilyn2485208958@gmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. xinzhao2006@gmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. cezh2002@yahoo.com.
authors.forename: Ce
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Forensic Medicine, Shanxi Medical University, 56# Xin Jian South Road, Taiyuan 030001, Shanxi, China. gdw195810@gmail.com.
authors.forename: Dawei
authors.initials: D
authors.lastname: Guo
mesh_terms: D017398:Alternative Splicing; D045744:Cell Line, Tumor; D051959:ELAV Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D039102:Poly(A)-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D051959:ELAV Proteins; D039102:Poly(A)-Binding Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C076751:TIAL1 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1