Potential Benefits in Inequality? The Protective Role of U1 snRNP

700 WordsApr 23, 20193 Pages
Potential Benefits in Inequality? The Protective Role of U1 snRNP Pre-mRNA in eukaryotes is spliced by the spliceosome, an RNA-protein complex, in which U1, U2, U4, U5 and U6 snRNPs are equal components. However, U1 is more abundant than other snRNPs in cells. U1 snRNP has been found to functions other than splicing, namely in protecting pre-mRNA from premature cleavage and polyadenylation. This protective role may account for its increased levels within cells. In eukaryotic cells, pre-mRNA undergoes extensive post-transcriptional modifications to become mature mRNA. The modifications to pre-mRNA include 5’ end capping, 3’ end cleavage and polyadenylation, and the splicing of introns (Gu and Lima, 2005). The spliceosome is a large…show more content…
It was seen that more introns were present in the U1 AMO cell transcripts than in the control, showing that splicing was inhibited, and so that U1 is critical to spliceosome activity. U1 AMO transfected cells were also compared to cells transfected with spliceostatin A (SSA), which inhibits splicing. As splicing was inhibited in both sets of cells, it would be expected that the same intron pattern would be seen, but this was not so. It was observed that in U1 AMO cells, introns tended to terminate early, often within the first 3-5 kb, and that in these transcripts, a polyadenylation sequence that is not encoded for by the genome was found at the 3’ end. The polyadenylation sequence was a consequence of a potential polyadenylation sequence (PAS) nearby. The differences between U1 AMO cell and SSA cell transcripts suggest that U1 snRNP acts to protect pre-mRNA from premature cleavage and polyadenylation (PCAP). To test this, a 5’ splice site close to a cryptic PAS was mutated. It was found that PCPA occurred both when U1 snRNP was available and when it was not, suggesting that the binding of U1 snRNP to 5’ splice sites directly helps to prevent PCPA. Interfering with U1 snRNP within eukaryotic cells affects splicing, as would be expected, as it is a key part of the spliceosome. However, it has been found that there are other, unexpected consequences. It has been seen that as well as its role in splicing

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