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.