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Modulation of msl-2 5′ splice site recognition by Sex-lethal

Published online by Cambridge University Press:  25 September 2001

PATRIK FÖRCH
Affiliation:
Gene Expression Programme, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany
LIVIA MERENDINO
Affiliation:
Gene Expression Programme, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany Present address: Department of Molecular Biology, University of Geneva, 30 Quai Ernest Ansermet, Ch-1211 Geneva 4, Switzerland.
CONCEPCIÓN MARTÍNEZ
Affiliation:
Gene Expression Programme, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany
JUAN VALCÁRCEL
Affiliation:
Gene Expression Programme, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany
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Abstract

The protein Sex-lethal (SXL) controls dosage compensation in Drosophila by inhibiting splicing and subsequently translation of male-specific-lethal-2 (msl-2) transcripts. We have previously shown that SXL blocks the binding of U2 auxiliary factor (U2AF) to the polypyrimidine (Py)-tract associated with the 3′ splice site of the regulated intron. We now report that a second pyrimidine-rich sequence containing 11 consecutive uridines immediately downstream from the 5′ splice site is required for efficient splicing inhibition by SXL. Psoralen-mediated crosslinking experiments suggest that SXL binding to this uridine-rich sequence inhibits recognition of the 5′ splice site by U1 snRNP in HeLa nuclear extracts. We also show that SXL interferes with the binding of the protein TIA-1 to the uridine-rich stretch. Because TIA-1 binding to this sequence is necessary for U1 snRNP recruitment to msl-2 5′ splice site and for splicing of this pre-mRNA, we propose that SXL antagonizes TIA-1 activity and thus prevents 5′ splice site recognition by U1 snRNP. Taken together with previous data, we conclude that efficient retention of msl-2 intron involves inhibition of early recognition of both splice sites by SXL.

Type
REPORT
Information
RNA , Volume 7 , Issue 9 , September 2001 , pp. 1185 - 1191
Copyright
2001 RNA Society

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