Research Article

Structural basis of pre-mRNA splicing

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Science  11 Sep 2015:
Vol. 349, Issue 6253, pp. 1191-1198
DOI: 10.1126/science.aac8159

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Structure and function of the spliceosome

When RNA is transcribed from DNA in the eukaryotic cell nucleus, the initial transcript includes noncoding introns that must be spliced out. This splicing is done by a complex macromolecular machine, the spliceosome, which comprises five small nuclear RNAs and more than 100 associated proteins. Now, two papers reveal insights into the structure and function of the yeast spliceosome. Yan et al. describe a high-resolution structure determined by electron microscopy of a spliceosome complex comprising four RNAs and 37 proteins. Hang et al. focus on the catalytic site and show how protein components anchor the transcribed RNA and allow sufficient flexibility to deliver RNA components involved in catalyzing the splicing reaction.

Science, this issue pp. 1182 and 1191


Splicing of precursor messenger RNA is performed by the spliceosome. In the cryogenic electron microscopy structure of the yeast spliceosome, U5 small nuclear ribonucleoprotein acts as a central scaffold onto which U6 and U2 small nuclear RNAs (snRNAs) are intertwined to form a catalytic center next to Loop I of U5 snRNA. Magnesium ions are coordinated by conserved nucleotides in U6 snRNA. The intron lariat is held in place through base-pairing interactions with both U2 and U6 snRNAs, leaving the variable-length middle portion on the solvent-accessible surface of the catalytic center. The protein components of the spliceosome anchor both 5′ and 3′ ends of the U2 and U6 snRNAs away from the active site, direct the RNA sequences, and allow sufficient flexibility between the ends and the catalytic center. Thus, the spliceosome is in essence a protein-directed ribozyme, with the protein components essential for the delivery of critical RNA molecules into close proximity of one another at the right time for the splicing reaction.

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