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Powering a two-stroke RNA engine

Nature Structural & Molecular Biology volume 14, pages 574–576 (2007)Cite this article

The spliceosome, the ribonucleoprotein complex that removes introns from precursor messenger RNAs, is thought to undergo conformational changes between two alternative states to catalyze the two steps of the splicing reaction, a model that resembles ribosomal transfer RNA decoding. Following very different strategies, two papers provide new insights into how core components of the spliceosome and regulatory factors containing arginine/serine-rich domains with RNA chaperone activity can facilitate these conformational changes.

A spatial rearrangement is necessary to reposition the splicing intermediates generated after the first catalytic step so that the reactive groups involved in the second step are brought closer together (Fig. 1). Understanding this repositioning may also help in identifying key spliceosomal components involved in catalysis. Two papers, one in this issue2 and one in the previous issue of Nature Structural & Molecular Biology3, now provide clues about the forces behind these transitions. Query and Konarska4 have proposed a model in which the spliceosome can adopt alternative, competing conformations for each catalytic step. Liu et al.3 provide additional evidence for this model by identifying two classes of mutants in Prp8, a key protein component of the spliceosome5, with opposite effects on each step of catalysis. Their results suggest that Prp8 modulates transitions between the alternative spliceosomal conformations. Such transitions depend upon remodeling of the network of interactions between the pre-mRNA and protein and RNA components of the spliceosome. On page 597 of this issue, Shen and Green2 now reveal how concerted rearrangements of RNA duplexes and arginine/serine-rich (RS) domains in splicing regulatory factors can aid progression from the first to the second catalytic step.

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Figure 1: The two chemical steps leading to intron removal and splicing of exons in pre-mRNA.
Figure 2: Schematic model of the spliceosome conformation at each catalytic step.

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Affiliations

  1. Josep Vilardell and Juan Valcárcel are at the Centre de Regulació Genòmica and Universitat Pompeu-Fabra, and Juan Valcárcel is at the Institució Catalana de Recerca i Estudis Avançats, Dr. Aiguader 88, 08003 Barcelona, Spain. josep.vilardell@crg.es juan.valcarcel@crg.es

    Josep Vilardell & Juan Valcárcel

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  1. Josep Vilardell
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  2. Juan Valcárcel
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Vilardell, J., Valcárcel, J. Powering a two-stroke RNA engine. Nat Struct Mol Biol 14, 574–576 (2007). https://doi.org/10.1038/nsmb0707-574

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