Abstract:
:The polypyrimidine tract near the 3' splice site is important for pre-mRNA splicing. Using pseudouridine incorporation and in vivo RNA-guided RNA pseudouridylation, we have identified two important uridines in the polypyrimidine tract of adenovirus pre-mRNA. Conversion of either uridine into pseudouridine leads to a splicing defect in Xenopus oocytes. Using a variety of molecular biology methodologies, we show that the splicing defect is due to the failure of U2AF(65) to recognize the pseudouridylated polypyrimidine tract. This negative impact on splicing is pseudouridine specific, as no effect is observed when the uridine is changed to other naturally occurring nucleotides. Given that pseudouridine favors a C-3'-endo structure, our results suggest that it is backbone flexibility that is key to U2AF binding. Indeed, locking the key uridine in the C-3'-endo configuration while maintaining its uridine identity blocks U2AF(65) binding and splicing. This pseudouridine effect can also be applied to other pre-mRNA polypyrimidine tracts. Thus, our work demonstrates that in vivo binding of U2AF(65) to a polypyrimidine tract requires a flexible RNA backbone.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Chen C,Zhao X,Kierzek R,Yu YTdoi
10.1128/MCB.00531-10subject
Has Abstractpub_date
2010-09-01 00:00:00pages
4108-19issue
17eissn
0270-7306issn
1098-5549pii
MCB.00531-10journal_volume
30pub_type
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