mRNA Splicing: Role of snRNAs

Abstract

Eukaryotic genomes code for many types of non‐coding RNAs (ncRNAs). One class of these ncRNAs is termed small nuclear RNAs (snRNAs). The snRNAs are, in turn, complexed with proteins to form small nuclear ribonucleoprotein particles (snRNPs). Many of these snRNPs are involved in the nuclear maturation of primary transcripts of messenger RNAs (mRNAs). Certain snRNAs are involved in the formation and function of spliceosomes, the large ribonucleoprotein structures in which pre‐mRNA splicing takes place. Most metazoan genomes contain two distinct types of spliceosomes which differ primarily in their snRNA composition. Biochemical, genetic and structural evidences suggest that snRNAs are core components of the catalytic centre of the spliceosomes.

Key Concepts

Eukaryotic genes often contain introns that are removed by RNA splicing.

  • RNA splicing takes place in large complexes of RNAs and proteins called spliceosomes.
  • Small nuclear RNAs (snRNAs) are essential parts of spliceosomes.
  • snRNAs are complexed with proteins to form snRNPs which are recruited to unspliced primary RNA transcripts and direct the formation of spliceosomes.
  • Evidence is growing that the snRNAs compose much if not all of the active site of the spliceosome suggesting that spliceosomes, like ribosomes, are RNA machines.

Keywords: pre‐mRNA splicing; ribonucleoproteins; spliceosome: introns; exons

Figure 1. Secondary structures of the spliceosomal snRNAs. Close‐set parallel lines indicate RNA stem structures held together by Watson–Crick base pairing. The 5′ end cap structures of the RNAs are indicated by blue balls for 2,2,7‐trimethylguanosine and pink balls for γ‐monomethylguanosine caps. Conserved regions of the snRNAs that are involved in RNA–RNA interactions in the spliceosome are shaded in yellow and the sites of Sm protein binding are shaded in pink.
Figure 2. The pre‐mRNA splicing reaction and snRNA interactions in the spliceosomes. (a) Schematic of the two‐step spliceosomal splicing reaction described in the text. (b) RNA–RNA interactions in the major, U2‐type spliceosome. Left: the initial interactions of the pre‐mRNA with U1 and U2 snRNPs. Right: the interactions in the mature spliceosome. Yellow bars indicate regions that interact by base pairing. The adenosine residue at the branch site is circled. (c) RNA–RNA interactions in the minor, U12‐type spliceosome.
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Further Reading

Gerbi SA, Borovjagin AV and Lange TS (2003) The nucleolus: a site of ribonucleoprotein maturation. Current Opinion in Cell Biology 15: 318–325.

Matera AG and Wang Z (2014) A day in the life of the spliceosome. Nature Reviews. Molecular Cell Biology 15: 108–121.

Nilsen TW (1998) RNA–RNA interactions in nuclear pre‐mRNA splicing. In: Simons RW and Grunberg‐Manago M (eds) RNA Structure and Function, pp. 279–307. New York: Cold Spring Harbor Laboratory Press.

Tycowski KT, Kolev NK, Conrad NK, Fok V and Steitz JA (2006) The ever‐growing world of small nuclear ribonucleoproteins. In: Gesteland RF, Cech TR and Atkins JF (eds) The RNA World, 3rd edn, pp. 327–368. New York: Cold Spring Harbor Laboratory Press.

Will CL and Luhrmann R (2011) Spliceosome structure and function. In: Atkins JF, Gesteland RF and Cech TR (eds) RNA Worlds, pp. 181–204. New York: Cold Spring Harbor Laboratory Press.

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Padgett, Richard A(Jun 2015) mRNA Splicing: Role of snRNAs. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000879.pub3]