TY - JOUR
T1 - Function of alternative splicing
AU - Stamm, Stefan
AU - Ben-Ari, Shani
AU - Rafalska, Ilona
AU - Tang, Yesheng
AU - Zhang, Zhaiyi
AU - Toiber, Debra
AU - Thanaraj, T. A.
AU - Soreq, Hermona
N1 - Funding Information:
This work was supported by the European Union (QLRT-CT-2001-02062).
PY - 2005/1/3
Y1 - 2005/1/3
N2 - Alternative splicing is one of the most important mechanisms to generate a large number of mRNA and protein isoforms from the surprisingly low number of human genes. Unlike promoter activity, which primarily regulates the amount of transcripts, alternative splicing changes the structure of transcripts and their encoded proteins. Together with nonsense-mediated decay (NMD), at least 25% of all alternative exons are predicted to regulate transcript abundance. Molecular analyses during the last decade demonstrate that alternative splicing determines the binding properties, intracellular localization, enzymatic activity, protein stability and posttranslational modifications of a large number of proteins. The magnitude of the effects range from a complete loss of function or acquisition of a new function to very subtle modulations, which are observed in the majority of cases reported. Alternative splicing factors regulate multiple pre-mRNAs and recent identification of physiological targets shows that a specific splicing factor regulates pre-mRNAs with coherent biological functions. Therefore, evidence is now accumulating that alternative splicing coordinates physiologically meaningful changes in protein isoform expression and is a key mechanism to generate the complex proteome of multicellular organisms.
AB - Alternative splicing is one of the most important mechanisms to generate a large number of mRNA and protein isoforms from the surprisingly low number of human genes. Unlike promoter activity, which primarily regulates the amount of transcripts, alternative splicing changes the structure of transcripts and their encoded proteins. Together with nonsense-mediated decay (NMD), at least 25% of all alternative exons are predicted to regulate transcript abundance. Molecular analyses during the last decade demonstrate that alternative splicing determines the binding properties, intracellular localization, enzymatic activity, protein stability and posttranslational modifications of a large number of proteins. The magnitude of the effects range from a complete loss of function or acquisition of a new function to very subtle modulations, which are observed in the majority of cases reported. Alternative splicing factors regulate multiple pre-mRNAs and recent identification of physiological targets shows that a specific splicing factor regulates pre-mRNAs with coherent biological functions. Therefore, evidence is now accumulating that alternative splicing coordinates physiologically meaningful changes in protein isoform expression and is a key mechanism to generate the complex proteome of multicellular organisms.
KW - Alternative splicing
KW - Binding properties
KW - Enzymatic activity
KW - Localization
KW - Review
UR - http://www.scopus.com/inward/record.url?scp=12344250822&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12344250822&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2004.10.022
DO - 10.1016/j.gene.2004.10.022
M3 - Review article
C2 - 15656968
AN - SCOPUS:12344250822
SN - 0378-1119
VL - 344
SP - 1
EP - 20
JO - Gene
JF - Gene
ER -