Biogenesis of small nuclear RNPs

Abstract

The nucleus contains a large number of metabolically stable, 60-450-nt-long small nuclear RNAs (snRNAs) that exist in the form of ribonucleoproteins (snRNPs) (Yu et al., 1999). Each snRNP is composed of an snRNA and a set of associated RNP proteins. Based on their function and intranuclear localization, mammalian snRNPs can be classified into three major classes. The U1, U2, U4, U5 and U6 major and the U11, U12, U4atac and U6atac minor spliceosomal snRNPs function in removal of premRNA introns and are predominantly nucleoplasmic (Lamond and Spector, 2003). More than 200 small nucleolar RNPs (snoRNPs) are present in the nucleolus, where they function mainly in the nucleolar maturation of cytoplasmic 18S, 5.8S and 28S rRNAs (Kiss, 2001; Terns and Terns, 2002). Finally, a recently discovered group of nuclear RNAs, termed small Cajal body RNPs (scaRNPs), accumulate in Cajal (coiled) bodies. The scaRNAs direct the site-specific 2′-O-ribose methylation and pseudouridylation of the RNA polymerase (Pol)-II-transcribed spliceosomal snRNAs (Darzacq et al., 2002). Biogenesis of snRNPs is a complex process that usually includes four major steps: (1) synthesis of a large precursor snRNA (pre-snRNA); (2) nucleolytic processing of the nascent pre-snRNA into mature-sized snRNA; (3) introduction of site-specific covalent nucleotide modifications; and (4) packaging of snRNA with RNP proteins. However, despite the apparent similarities, the various classes of snRNP follow different biosynthetic…