Structural basis for the dual RNA-recognition modes of human Tra2-? RRM.

ABSTRACT: Human Transformer2-? (hTra2-?) is an important member of the serine/arginine-rich protein family, and contains one RNA recognition motif (RRM). It controls the alternative splicing of several pre-mRNAs, including those of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Accordingly, the RRM of hTra2-? specifically binds to two types of RNA sequences [the CAA and (GAA)(2) sequences]. We determined the solution structure of the hTra2-? RRM (spanning residues Asn110-Thr201), which not only has a canonical RRM fold, but also an unusual alignment of the aromatic amino acids on the ?-sheet surface. We then solved the complex structure of the hTra2-? RRM with the (GAA)(2) sequence, and found that the AGAA tetra-nucleotide was specifically recognized through hydrogen-bond formation with several amino acids on the N- and C-terminal extensions, as well as stacking interactions mediated by the unusually aligned aromatic rings on the ?-sheet surface. Further NMR experiments revealed that the hTra2-? RRM recognizes the CAA sequence when it is integrated in the stem-loop structure. This study indicates that the hTra2-? RRM recognizes two types of RNA sequences in different RNA binding modes.

SUBMITTER: Tsuda K 

PROVIDER: S-EPMC3045587 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature