TIS11 family proteins and their roles in posttranscriptional gene regulation

Abstract

Posttranscriptional regulation of gene expression of mRNAs containing adenine-uridine rich elements (AREs) in their 3' untranslated regions is mediated by a number of different proteins that interact with these elements to either stabilise or destabilise them. The present review concerns the TPA-inducible sequence 11 (TIS11) protein family, a small family of proteins, that appears to interact with ARE-containing mRNAs and promote their degradation. This family of proteins has been extensively studied in the past decade. Studies have focussed on determining their biochemical functions, identifying their target mRNAs, and determining their roles in cell functions and diseases.

Figure 1

Pathways and major components of ARE-mediated mRNA decay by TIS11 proteins. TIS11 protein binds to the ARE sequence in the 3′ UTR and recruits deadenylases either directly (hCcr4) or indirectly (PARN). Deadenylated mRNA can be recruited by the exosome, a multiprotein structure containing proteins such as Rrp4, Rrp40, Rrp41, and PM-Scl75 that form the 3′ to 5′ exoribonuclease complex. Decapping of mRNA can follow deadenylation mediated by decapping enzymes such as Dcp1 and Dcp2 and degradation of mRNA can then be mediated by the 5′ to 3′ Xrn1 exonuclease.