Differential Effects of Sumoylation on Transcription and Alternative Splicing by Transcription Elongation Regulator 1 (TCERG1)

Noemí Sánchez-Hernández,Miguel Sánchez-Álvarez,Marta Montes,Carlos Suñé,Cristina Hernández-Munain

doi:10.1074/jbc.m109.063750

Abstract

Modification of proteins by small ubiquitin-like modifier (SUMO) is emerging as an important control of transcription and RNA processing. The human factor TCERG1 (also known as CA150) participates in transcriptional elongation and alternative splicing of pre-mRNAs. Here, we report that SUMO family proteins modify TCERG1. Furthermore, TCERG1 binds to the E2 SUMO-conjugating enzyme Ubc9. Two lysines (Lys-503 and Lys-608) of TCERG1 are the major sumoylation sites. Sumoylation does not affect localization of TCERG1 to the splicing factor-rich nuclear speckles or the alternative splicing function of TCERG1. However, mutation of the SUMO acceptor lysine residues enhanced TCERG1 transcriptional activity, indicating that SUMO modification negatively regulates TCERG1 transcriptional activity. These results reveal a regulatory role for sumoylation in controlling the activity of a transcription factor that modulates RNA polymerase II elongation and mRNA alternative processing, which are discriminated differently by this post-translational modification.

Highlights

Splicing and transcriptional elongation are physically and functionally interconnected processes [1, 2]
TCERG1 Is Modified by small ubiquitin-like modifier (SUMO)-1 and SUMO-2/3 in Vivo— TCERG1 potentially couples transcription and mRNA processing; the molecular mechanisms by which TCERG1 modulates transcriptional elongation and splicing remain to be elucidated
We demonstrate that TCERG1 is a substrate for SUMO-1 and SUMO-2/3 conjugation

Summary

Introduction

Splicing and transcriptional elongation are physically and functionally interconnected processes [1, 2]. The results of the in vitro binding assay revealed a direct interaction between hUbc9 and the amino-terminal 662 amino acids of TCERG1 (Fig. 1F, bottom panel), supporting the conclusion that this region of TCERG1 contains required sequences for proper interaction with the sumoylation machinery and conjugation with SUMO.

Results

Conclusion