原创力文档reprogramming of 3′ untranslated regions of mrnas by alternative polyadenylation in generation of pluripotent stem cells from different cell types重组的mrna 3u2032未翻译区替代聚腺苷酸化生成不同细胞类型的多能干细胞.pdfVIP
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reprogramming of 3′ untranslated regions of mrnas by alternative polyadenylation in generation of pluripotent stem cells from different cell types重组的mrna 3u2032未翻译区替代聚腺苷酸化生成不同细胞类型的多能干细胞
Reprogramming of 39 Untranslated Regions of mRNAs by
Alternative Polyadenylation in Generation of Pluripotent
Stem Cells from Different Cell Types
Zhe Ji, Bin Tian*
Department of Biochemistry and Molecular Biology, Graduate School of Biomedical Sciences and New Jersey Medical School, University of Medicine and Dentistry of New
Jersey, Newark, New Jersey, United States of America
Abstract
Background: The 3 9 untranslated regions (39UTRs) of mRNAs contain cis elements involved in post-transcriptional
regulation of gene expression. Over half of all mammalian genes contain multiple polyadenylation sites that lead to
different 39UTRs for a gene. Studies have shown that the alternative polyadenylation (APA) pattern varies across tissues, and
is dynamically regulated in proliferating or differentiating cells. Generation of induced pluripotent stem (iPS) cells, in which
differentiated cells are reprogrammed to an embryonic stem (ES) cell-like state, has been intensively studied in recent years.
However, it is not known how 39UTRs are regulated during cell reprogramming.
Methods/Main Findings: Using a computational method that robustly examines APA across DNA microarray data sets, we
analyzed 39UTR dynamics in generation of iPS cells from different cell types. We found that 39UTRs shorten during
reprogramming of somatic cells, the extent of which depends on the type of source cell. By contrast, reprogramming of
spermatogonial cells involves 39UTR lengthening. The alternative polyadenylation sites that are highly responsive to change
of cell state in generation of iPS cells are also highly regulated during embryonic development in opposite directions.
Compared with other sites, they are more conserved, can lead to longer alternative 39UTRs, and are associated with more cis
elements for pol
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