Bioscience Chapter Database :: 3635 Chapters Now Online

Chapter category: RNA

The Coupling of Alternative Splicing and Nonsense‑Mediated mRNA Decay

This chapter appears in the following book:

Alternative Splicing
in the Postgenomic Era

Edited by: Benjamin J. Blencowe and Brenton R. Graveley
ISBN: 978-0-387-77373-5
» Get more information about this book at landesbioscience.com «

Chapter authors:
Liana F. Lareau, Angela N. Brooks, David A.W. Soergel, Qi Meng and Steven E. Brenner


[+] view image
Most human genes exhibit alternative splicing, but not all alternatively spliced transcripts produce functional proteins. Computational and experimental results indicate that a substantial fraction of alternative splicing events in humans result in mRNA isoforms that harbor a premature termination codon (PTC). These transcripts are predicted to be degraded by the nonsense‑mediated mRNA decay (NMD) pathway. One explanation for the abundance of PTC‑containing isoforms is that they represent splicing errors that are identified and degraded by the NMD pathway. Another potential explanation for this startling observation is that cells may link alternative splicing and NMD to regulate the abundance of mRNA transcripts. This mechanism, which we call “Regulated Unproductive Splicing and Translation” (RUST), has been experimentally shown to regulate expression of a wide variety of genes in many organisms from yeast to human. It is frequently employed for autoregulation of proteins that affect the splicing process itself. Thus, alternative splicing and NMD act together to play an important role in regulating gene expression.

Liana F. Lareau
Department of Molecular and Cell Biology, University of California-Berkeley

Angela N. Brooks
Department of Molecular and Cell Biology, University of California-Berkeley

David A.W. Soergel
Biophysics Graduate Group, University of California-Berkeley

Qi Meng
Department of Plant and Microbial Biology, University of California-Berkeley

Steven E. Brenner
Departments of Plant and Microbial Biology and Molecular and Cell Biology, University of California-Berkeley

» Download Open Access Chapter



Additional chapters from this book:

Coupling Transcription and Alternative Splicing

Alberto R. Kornblihtt

Alternative splicing regulation not only depends on the interaction of splicing factors with splicing enhancers and silencers in the pre‑mRNA, but also on the coupling between transcription and ...

Searching for Splicing Motifs

Lawrence A. Chasin

Intron removal during pre‑mRNA splicing in higher eukaryotes requires the accurate identification of the two splice sites at the ends of the exons, or exon definition. The sequences constituting...

Nuclear Organization and Splicing Control

Maria Carmo-Fonseca and Célia Carvalho

Although major splicing regulatory mechanisms rely on the presence of cis‑acting sequence elements in the precursor messenger RNA (pre‑mRNA) to which specific protein and RNA factors bind,...

Alternative Splicing in Disease

James P. Orengo and Thomas A. Cooper

Alternative splicing is a major source of diversity in the human proteome. The regulation of alternative splicing modulates the composition of this diversity to fulfill the physiological requirements ...

SR Proteins and Related Factors in Alternative Splicing

Shengrong Lin and Xiang-Dong Fu

SR proteins are a family of RNA binding proteins that contain a signature RS domain enriched with serine/arginine repeats. The RS domain is also found in many other proteins, which are collectively re...

Regulation of Alternative Splicing by Signal Transduction Pathways

Kristen W. Lynch

Alternative splicing is now recognized as a ubiquitous mechanism for controlling gene expression in a tissue‑specific manner. A growing body of work from the past few years has begun to also hig...

Relating Alternative Splicing to Proteome Complexity and Genome Evolution

Yi Xing and Christopher Lee

Prior to genomics, studies of alternative splicing primarily focused on the function and mechanism of alternative splicing in individual genes and exons. This has changed dramatically since the late 1...

hnRNP Proteins and Splicing Control

Rebeca Martinez-Contreras, Philippe Cloutier, Lulzim Shkreta, Jean‑François Fisette, Timothée Revil and Benoit Chabot

Proteins of the heterogeneous nuclear ribonucleoparticles (hnRNP) family form a structurally diverse group of RNA binding proteins implicated in various functions in metazoans. Here we discuss recent ...

Complex Alternative Splicing

Jung Woo Park and Brenton R. Graveley

Alternative splicing is a powerful means of controlling gene expression and increasing protein diversity. Most genes express a limited number of mRNA isoforms, but there are several examples of genes ...

Technologies for the Global Discovery and Analysis of Alternative Splicing

John A. Calarco, Arneet L. Saltzman, Joanna Y. Ip and Benjamin J. Blencowe

During the past ~20 years, studies on alternative splicing (AS) have largely been directed at the identification and characterization of factors and mechanisms responsible for the control of splice si...

Functional and Mechanistic Insights From Genome‑Wide Studies of Splicing Regulation in the Brain

Jernej Ule and Robert B. Darnell

We review here results arising from the systematic functional analysis of Nova, a neuron‑specific RNA binding protein targeted in an autoimmune neurological disorder associated with cancer. We h...

Spliceosome Assembly and Composition

Arianne J. Matlin and Melissa J. Moore

Cells control alternative splicing by modulating assembly of the pre‑mRNA splicing machinery at competing splice sites. Therefore, a working knowledge of spliceosome assembly is essential for un...

The Coupling of Alternative Splicing and Nonsense‑Mediated mRNA Decay

Liana F. Lareau, Angela N. Brooks, David A.W. Soergel, Qi Meng and Steven E. Brenner

Most human genes exhibit alternative splicing, but not all alternatively spliced transcripts produce functional proteins. Computational and experimental results indicate that a substantial fraction of...


SIGN IN

Email:


Password:


lost password?




[ Home | Authors | Editors | Custom Books | Chapter Reprints | Subscribe | Contact | Biotoons ]