Small Nuclear RNAs and RNA Processing

Abstract

I. Summary Ribosomal RNA, transfer RNA, and messenger RNAs, which comprise about 99% of the cellular RNA, are part of the protein-synthesizing machinery. Many studies in the last 15 years have established the presence of another class of RNA, “small nuclear RNAs” (snRNAs) that account for 0.1-1% of the total cellular RNA. There is evidence for at least 15 distinct small RNAs in rat and human cells. Of these, six (designated Ul- to U6-RNAs) are capped, metabolically stable, synthesized by polymerase II, present as ribonucleoprotein particles, and present in concentrations comparable to that of ribosomes. U3-RNA, found only in the nucleolus, is associated with preribosomal RNA and is involved in maturation of ribosomal RNAs, although the precise mechanism is not known. U1-, U2-, U4-, U5-, and U6-RNPs, found in nucleoplasm, are in part associated with hnRNP particles and are implicated in messenger RNA transport and processing; the detailed mechanism(s) are under study. The discovery that patients with autoimmune diseases produce antibodies against RNP particles containing small nuclear RNAs made improved methods for studies on small RNPs available to researchers in many disciplines. The availability of these immunological reagents for selective immunoprecipitation of specific U-snRNPs and other snRNPs offers a powerful approach to study their structures, intracellular localization, and function. In addition, the attractive hypothesis that snRNAs, like Ul-RNA, may be involved in properly aligning splice junctions, of pre-mRNA, brought snRNAs to the attention of many researchers. Unlike the capped U-snRNAs, which are transcribed by RNA polymerase II, the noncapped RNAs are transcribed by RNA polymerase III; they have diverse functions. Cytoplasmic 7 S RNA is an integral part of the “signal recognition particle” involved in synthesis and transport of secretory proteins (181a). RNase-P (EC 3.1.26.5) RNA has been reported (200, 201 ) to be part of an RNP particle involved in processing precursor tRNAs. P-snRNA is implicated in making chromatin accessible for crossing-over during meiosis (34) , and CEH-RNA is thought to induce embryonic heart-cell differentiation (198). In addition, several RNAs, including 4.5 and 4.5 SI, 6 S, 7 S RNAs, exhibit homologies to reiterated DNA sequences, whose significance is not understood. Although the structures of the small RNAs are now well defined, much remains to be learned about their relationship to proteins in snRNP particles and the functions of the snRNP particles.