Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MRNA profiles following TUT knock-down in HeLa


ABSTRACT: The precise control of microRNA (miRNA) biogenesis is important for various cellular functions, and its dysregulation is often associated with human diseases. We previously reported that Terminal uridylyl transferase 4 (TUT4) down-regulates let-7 miRNA biogenesis by oligo-uridylating let-7 precursor (pre-let-7) in mouse embryonic stem cells and that a pluripotency marker Lin28 promotes a processivity of TUT4. Here we find that TUT4 positively controls let-7 biogenesis by adding a uridine residue to the 3’ end of pre-let-7 in the absence of Lin28. Such mono-uridylation enhances Dicer processing by generating an optimal end structure of pre-let-7 for Dicer recognition and may protect pre-miRNA from trimming. Moreover, TUT7, TUT4 and TUT2 redundantly regulate pre-let-7 processing and simultaneous knock down of these TUTs leads to the decrease of mature let-7 and the accumulation of pre-let-7 in cells. This study provides a novel regulation mechanism of miRNA biogenesis, which may function in development and tumorigenesis. HeLa cells were transfected with siRNA two times over a 4~5 day period.

ORGANISM(S): Homo sapiens

SUBMITTER: Hyeshik Chang 

PROVIDER: E-GEOD-40228 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs.

Heo Inha I   Ha Minju M   Lim Jaechul J   Yoon Mi-Jeong MJ   Park Jong-Eun JE   Kwon S Chul SC   Chang Hyeshik H   Kim V Narry VN  

Cell 20121011 3


RNase III Drosha initiates microRNA (miRNA) maturation by cleaving a primary miRNA transcript and releasing a pre-miRNA with a 2 nt 3' overhang. Dicer recognizes the 2 nt 3' overhang structure to selectively process pre-miRNAs. Here, we find that, unlike prototypic pre-miRNAs (group I), group II pre-miRNAs acquire a shorter (1 nt) 3' overhang from Drosha processing and therefore require a 3'-end mono-uridylation for Dicer processing. The majority of let-7 and miR-105 belong to group II. We ident  ...[more]

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