Accession Number : AD1050203


Title :   Characterization of mTOR-Responsive Truncated mRNAs in Cell Proliferation


Descriptive Note : Technical Report,01 Jul 2016,30 Jun 2017


Corporate Author : Regents of the University of Minnesota Minneapolis United States


Personal Author(s) : Yong, Jeongsik


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050203.pdf


Report Date : 01 Jul 2017


Pagination or Media Count : 14


Abstract : Defective Tuberous Sclerosis Complex (TSC) 1 or 2 gene leads to deregulated mTOR activation and consequent cell proliferation/growth.Thus, studying the mTOR pathway at a molecular level is fundamental to understand TSC pathogenesis. We recently discovered genome-widealterations of polyadenylation site in mRNAs. These findings identify a previously uncharacterized role for mTOR in modulating 3-UTR length of mRNAs by alternative polyadenylation (APA). Another outcome of APA in the mTOR-activated transcriptome is an earlytermination of mRNA transcription to produce truncated mRNAs with polyadenylation in upstream introns/exons. Truncated mRNAscontain distinct molecular signatures at both RNA and protein levels: the new 3-end of mRNAs is from introns (intronic 3-end) and itgenerates a brand new C-terminus protein sequence encoded from introns. Thus, it is likely that activation of mTOR adds new molecularsignatures to functional transcriptome and proteome by alternating polyandeylation. In this reporting period, we profiled truncated mRNAsand their protein products using RNA-seq, 3-end seq, high capacity mass spectrometry and bioinformatics tools. We developed a newbioinformatics tool to integrate RNA-seq and 3-end seq and this tool makes it possible to reveal truncated mRNAs genome-wide. In silicoproteogenomics database for intron-coded C-terminus of truncated proteins has been developed and used for search of truncated proteins.Additional new software to find unannoated truncated mRNAs are under development.


Descriptors :   sclerosis , ribonucleic acids , genes , proteins , rna sequence analysis , algorithms , computer programs , biomedical information systems


Subject Categories : Medicine and Medical Research
      Biochemistry
      Computer Programming and Software


Distribution Statement : APPROVED FOR PUBLIC RELEASE