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发布于:2019-6-4 19:19:05  访问:28 次 回复: 篇
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Because the impact of SUB2 on repeat instability is MUD2 independent, we suggest that free of charge Sub2p can have OxitriptanTechnical Information functions outdoors of pre-mRNA splicing. Because the effect of SUB2 on repeat instability is MUD2 independent, we recommend that free Sub2p can have functions outdoors of pre-mRNA splicing. Among these functions could possibly be PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24247322 to aid in transcription elongation as an RNA helicase. We suggest that for the duration of elongation Hpr1p aids in avoiding transcription pauses, possibly by removing accumulated secondary structures within the nascent RNA. In the absence of Hpr1p, readily available no cost Sub2p may be able to remove transcription blocks by means of the RNA helicase activity, removing the secondary structure. This could clarify the mutual high-copy-number suppression by HPR1 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21795619 and SUB2 plus the absence of synergism or additivity in recombination rates. The transcription blocks, if not removed by Hpr1p or Sub2p, are eventually processed into recombination substrates. Certainly, it has been proposed that deletions in between direct repeats may perhaps result in the convergence of a stalled transcription complicated with a DNA replication complex (32, 45). We suggest that the action of Hpr1p is through elongation and not splicing, as no defect in splicing is observed inside the hpr1 mutant (37). Sub2p may be straight involved in genome stability. An intriguing possibility is the fact that Sub2p doesn‘t function exclusively in splicing but may have a far more general function in resolving RNA structures, a function that could possibly be Mud2 independent. Evidence strongly suggests that transcription by RNA polymerase II and pre-mRNA processing are temporally coupled (26, 29). In addition, the biggest subunit of RNA polymerase II has been located to physically associate with spliceosome elements, including SR proteins and snRNPs (28, 46, 51). For that reason, it‘s affordable to speculate that Sub2p might not be particularly targeted to intron-containing genes but is delivered to all genes transcribed by RNA polymerase II. A unifying hy-pothesis would be that Sub2p is tethered for the splicing apparatus by means of Mud2p and for the transcription apparatus through other proteins and functions to unwind a diversity of problematic RNA structures. The lethality observed within a sub2 strain may well then be straight related to a loss of Sub2p function in splicing, when the hyperrecombination phenotype displayed in the sub2 1 YCp-SUB2 strains could outcome from an effect on a additional common aspect of RNA production. The level of free Sub2 protein can be controlled by the volume of Mud2 protein within the pre-mRNA-U1 complex.ACKNOWLEDGMENTS We‘re really grateful to Alan Weiner and Robert J. Lake for discussions and important reading from the manuscript. We are particularly to grateful to Christine Guthrie and Amy Kistler for offering the sub2 conditional allele plasmids and for communication of unpublished final results. We thank Judith Jaehning for plasmids and discussion of unpublished benefits. This function was supported by NIH grant GM30439. Computing was supported by NSF grant BIR-9318128.REFERENCES 1. Abovich, N., X. C. Liao, and M. Rosbash. 1994. The yeast MUD2 protein: an interaction with PRP11 defines a bridge in between commitment complexes and U2 snRNP addition.
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