Role In Splicing Research Articles

Small RNAs in HnRNP fibrils and their possible function in splicing.

Several arguments are in favor of a function of snRNA in the processing of premessenger RNA. A large fraction of snRNA is localized in hnRNP which are assumed to be the site of processing. The different snRNA species are not bound to hnRNP in a unique manner but are associated with both proteins and hnRNA which suggests the possibility of metabolic exchanges in the course of processing. There is approximately 1-2 molecules of snRNA per individual hnRNP. We reexamined the possibility that U1A RNA might serve for the alignment of the extremities of the intron sequences of premessenger RNA insuring correct condition for cutting and splicing. We found that only a UCCA (3' leads to 5') sequence at position 8-11 of U1A RNA was complementary to an AG-GU (5' leads to 3') around a putative splice point for 69 different introns sequenced so far. On the basis of secondary structure of U1A RNA, the UCCA sequence would be available for hybridization. The UCCA sequence is also present in U2 RNA and 4.5 S RNAI. It might associate with AG-GU in a manner similar to that of codon-anticodon, the stability of the complex being insured by the configuration of hnRNP. The possible formation of larger hybrids stable by themselves is unlikely upon examination of the nucleotide sequence of various introns adjacent to the splice point. As there is no direct experimental evidence for the function of snRNA in splicing, there considerations are speculative at the present time. The possibility that adenovirus encoded VA RNA would play a role in splicing was also examined. Various arguments suggest that this possibility is rather remote.

Binding of adenovirus VA RNA to mRNA: a possible role in splicing?

Most, though not all, of the messenger RNAs of higher cells are composed of transcripts from two or more non-contiguous DNA segments that are 'spliced' together by mechanisms which are poorly understood. There has been recent speculation that small RNA molecules may play a part in the splicing reaction, acting as templates or adaptors to stabilize the appropriate conformation of a precursor RNA. Adenovirus-2 codes for two low molecular weight RNAs, the virus-associate (VA) RNAs I and II, major and minor species, respectively. These RNAs are about 160 nucleotides long and have both been sequenced. They originate from closely spaced genes which are transcribed by RNA polymerase III, but have not been definitively associated with any function. We have shown previously that a fraction of the VA RNA of infected cells is complexed with high molecular weight RNA in a denaturation-sensitive fashion. Results presented here show that the VA RNAs bind to unfractionated late virus mRNA and to a cloned copy of a single mRNA species, but not to corresponding cloned segments of viral genomic DNA. It is suggested that VA RNA may act as a template in the splicing reaction.