The Splicing Regulator TIA-1 Interacts with U1-C to Promote U1 SnRNP Recruitment to 5' Splice Sites

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Dec 18

PMID 12486009

Citations 128

Authors

Patrik Forch

Oscar Puig

Concepcion Martinez

Bertrand Seraphin

Juan Valcarcel

Affiliations

Soon will be listed here.

Abstract

The U1 small nuclear ribonucleoprotein (U1 snRNP) binds to the pre-mRNA 5' splice site (ss) at early stages of spliceosome assembly. Recruitment of U1 to a class of weak 5' ss is promoted by binding of the protein TIA-1 to uridine-rich sequences immediately downstream from the 5' ss. Here we describe a molecular dissection of the activities of TIA-1. RNA recognition motifs (RRMs) 2 and 3 are necessary and sufficient for binding to the pre-mRNA. The non- consensus RRM1 and the C-terminal glutamine-rich (Q) domain are required for association with U1 snRNP and to facilitate its recruitment to 5' ss. Co-precipitation experiments revealed a specific and direct interaction involving the N-terminal region of the U1 protein U1-C and the Q-rich domain of TIA-1, an interaction enhanced by RRM1. The results argue that binding of TIA-1 in the vicinity of a 5' ss helps to stabilize U1 snRNP recruitment, at least in part, via a direct interaction with U1-C, thus providing one molecular mechanism for the function of this splicing regulator.

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