Splicing factor Prp8 governs U4/U6 RNA unwinding during activation of the spliceosome.

Abstract:

:The pre-mRNA 5' splice site is recognized by the ACAGA box of U6 spliceosomal RNA prior to catalysis of splicing. We previously identified a mutant U4 spliceosomal RNA, U4-cs1, that masks the ACAGA box in the U4/U6 complex, thus conferring a cold-sensitive splicing phenotype in vivo. Here, we show that U4-cs1 blocks in vitro splicing in a temperature-dependent, reversible manner. Analysis of splicing complexes that accumulate at low temperature shows that U4-cs1 prevents U4/U6 unwinding, an essential step in spliceosome activation. A novel mutation in the evolutionarily conserved U5 snRNP protein Prp8 suppresses the U4-cs1 growth defect. We propose that wild-type Prp8 triggers unwinding of U4 and U6 RNAs only after structurally correct recognition of the 5' splice site by the U6 ACAGA box and that the mutation (prp8-201) relaxes control of unwinding.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Kuhn AN,Li Z,Brow DA

doi

10.1016/s1097-2765(00)80175-6

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

65-75

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(00)80175-6

journal_volume

3

pub_type

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