Function of quaking in myelination

Regulation of alternative splicing

Jiang I. Wu, Robyn Reed, Paula J. Grabowski, Karen Artzt

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Proteomic diversity is frequently achieved by alternative RNA-splicing events that can be fine-tuned in tissue-specific and developmentally regulated ways. Understanding this type of genetic regulation is compelling because of the extensive complexity of alternative splicing found in the nervous system. quaking (qk), one of the classical mouse dysmyelination mutants, is defective for the expression of myelin-associated glycoprotein (MAG), and the misregulation of MAG pre-mRNA alternative splicing is implicated as a causal factor. The qk locus encodes several RNA-binding proteins with heterogeneous nuclear ribonucleoprotein K-type homology, a characteristic of several known alternative splicing regulators. Here we test the nuclear-localized qk isoform (QKI-5) for its ability to regulate alternative splicing of MAG pre-mRNA in transient coexpression assays. QKI-5 exhibits properties of a negative regulator of MAG exon 12 alternative splicing. An intronic sequence element required for the repressive function and binding of QKI-5 is also identified. Direct evidence for irregularities in alternative splicing of MAG and other myelin protein transcripts in the qk mouse is demonstrated.

Original languageEnglish (US)
Pages (from-to)4233-4238
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number7
DOIs
StatePublished - Apr 2 2002

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Alternative Splicing
Myelin-Associated Glycoprotein
RNA Precursors
Quaking Mice
Heterogeneous-Nuclear Ribonucleoprotein K
Myelin Proteins
RNA-Binding Proteins
Proteomics
Nervous System
Exons
Protein Isoforms

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "Proteomic diversity is frequently achieved by alternative RNA-splicing events that can be fine-tuned in tissue-specific and developmentally regulated ways. Understanding this type of genetic regulation is compelling because of the extensive complexity of alternative splicing found in the nervous system. quaking (qk), one of the classical mouse dysmyelination mutants, is defective for the expression of myelin-associated glycoprotein (MAG), and the misregulation of MAG pre-mRNA alternative splicing is implicated as a causal factor. The qk locus encodes several RNA-binding proteins with heterogeneous nuclear ribonucleoprotein K-type homology, a characteristic of several known alternative splicing regulators. Here we test the nuclear-localized qk isoform (QKI-5) for its ability to regulate alternative splicing of MAG pre-mRNA in transient coexpression assays. QKI-5 exhibits properties of a negative regulator of MAG exon 12 alternative splicing. An intronic sequence element required for the repressive function and binding of QKI-5 is also identified. Direct evidence for irregularities in alternative splicing of MAG and other myelin protein transcripts in the qk mouse is demonstrated.",
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Function of quaking in myelination : Regulation of alternative splicing. / Wu, Jiang I.; Reed, Robyn; Grabowski, Paula J.; Artzt, Karen.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 7, 02.04.2002, p. 4233-4238.

Research output: Contribution to journalArticle

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T2 - Regulation of alternative splicing

AU - Wu, Jiang I.

AU - Reed, Robyn

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AU - Artzt, Karen

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