Tau Exons 2 and 10, Which Are Misregulated in Neurodegenerative Diseases, Are Partly Regulated by Silencers Which Bind a SRp30c·SRp55 Complex That Either Recruits or Antagonizes htra2β1

Yingzi Wang,Junning Wang,Lei Gao,Robert Lafyatis,Stefan Stamm,Athena Andreadis

doi:10.1074/jbc.m413846200

Abstract

Tau Exons 2 and 10, Which Are Misregulated in Neurodegenerative Diseases, Are Partly Regulated by Silencers Which Bind a SRp30c·SRp55 Complex That Either Recruits or Antagonizes htra2β1

Highlights

Alternative splicing is a versatile and widespread mechanism for generating multiple mRNAs from a single transcript [1, 2]
On the trans side of regulation, mammalian splicing regulators mostly belong to two superfamilies, the serine/argininerich (SR)1 proteins and the heterogeneous ribonuclear proteins, neither of which is exclusively involved in alternative splicing [12, 13]
Several mammalian splicing factors are enhanced in or restricted to neurons, among them htra2␤3, a splicing variant of htra2␤1 [14]. It appears that the exquisite calibration of mammalian alternative splicing is primarily achieved by SR and heterogeneous ribonuclear proteins (hnRNPs) proteins, which show distinct tissue and developmental ratios, despite their ubiquitous distribution [15, 16]

Summary

Introduction

Alternative splicing is a versatile and widespread mechanism for generating multiple mRNAs from a single transcript [1, 2]. On the trans side of regulation, mammalian splicing regulators mostly belong to two superfamilies, the serine/argininerich (SR) proteins and the heterogeneous ribonuclear proteins (hnRNPs), neither of which is exclusively involved in alternative splicing [12, 13]. The former are components of the spliceosome, whereas the latter are involved in pre-mRNA transport, RNA stability, and translational regulation. The C terminus of the tau protein contains four imperfect repeats (encoded by exons 9 –12) that act as microtubule binding domains [21]

Results

Discussion

Conclusion