Commitment to splice site pairing coincides with A complex formation.

Sharlene R Lim; Klemens J Hertel

doi:10.1016/j.molcel.2004.06.025

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Commitment to splice site pairing coincides with A complex formation.

Sharlene R Lim·Klemens J Hertel

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Abstract

Differential recognition of exons by the spliceosome regulates gene expression and exponentially increases the complexity of metazoan proteomes. After definition of the exons, the spliceosome is activated by a series of sequential structural rearrangements. Formation of the first ATP-independent spliceosomal complex commits the pre-mRNA to the general splicing pathway. However, the time at which a commitment to a specific splice site choice and pairing is made is unknown. Here, we demonstrate that alternative splicing patterns are irreversibly chosen at a kinetic step different from the ATP-independent commitment to splicing. Splice sites become committed at the first ATP-dependent spliceosomal complex when rearrangements lock U2 snRNP onto the pre-mRNA. Thus, commitment to the splicing pathway and commitment to splice site pairing are separate steps during spliceosomal assembly, and ATP hydrolysis drives the irreversible juxtaposition of exons within the spliceosome.

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Animals Humans Kinetics RNA Splicing RNA, Messenger Spliceosomes Journal Article Research Support, U.S. Gov't, P.H.S.

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Sharlene R Lim, Klemens J Hertel. 2004-08-13. Commitment to splice site pairing coincides with A complex formation.. https://doi.org/10.1016/j.molcel.2004.06.025

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