Repositioning of the reaction intermediate within the catalytic center of the spliceosome

Maria M. Konarska, Josep Vilardell, Charles C. Query

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Conformational change within the spliceosome is required between the first catalytic step of pre-mRNA splicing, when the branch site attacks the 5′ splice site (SS), and the second step, when the 5′ exon attacks the 3′SS. Little is known, however, about repositioning of the reaction substrates during this transition. Whereas the 5′SS is positioned for the first step by pairing with the invariant U6 snRNA-ACAGAG site, we demonstrate that this pairing interaction must be disrupted to allow transition to the second step. We propose that removal of the branch structure from the catalytic center is in competition with binding of the 3′SS substrate for the second step. Changes in the relative occupancy of first and second step substrates at the catalytic center alter efficiency of the two steps of splicing, allowing use of suboptimal intron sequences and thereby altering substrate selectivity.

Original languageEnglish (US)
Pages (from-to)543-553
Number of pages11
JournalMolecular Cell
Volume21
Issue number4
DOIs
StatePublished - Feb 17 2006

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Spliceosomes
RNA Splice Sites
RNA Precursors
Introns
Exons
U6 small nuclear RNA

ASJC Scopus subject areas

  • Molecular Biology

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Repositioning of the reaction intermediate within the catalytic center of the spliceosome. / Konarska, Maria M.; Vilardell, Josep; Query, Charles C.

In: Molecular Cell, Vol. 21, No. 4, 17.02.2006, p. 543-553.

Research output: Contribution to journalArticle

Konarska, Maria M. ; Vilardell, Josep ; Query, Charles C. / Repositioning of the reaction intermediate within the catalytic center of the spliceosome. In: Molecular Cell. 2006 ; Vol. 21, No. 4. pp. 543-553.
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