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microRNA nuclear import machinery elucidated on molecular level

miRNA may regulate gene expression in the nucleus

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Graduate School of Science / Faculty of Science
2012/12/05

TNRC6A protein translocates from the cytoplasm to the nucleus via its own nuclear localization signal (NLS) and exports from the nucleus to the cytoplasm by its nuclear export signal (NES).
© Kenji Nishi and Kumiko Ui-Tei

TNRC6A brings miRNAs into the nucleus via its interaction with Ago. In the cytoplasm, a miRNA-Ago-TNRC6A complex induces translational repression and/or mRNA degradation. In the nucleus, it was suggested that its complex might inhibit the expression of target RNA, but other functions remain unknown.

MicroRNAs (miRNAs) are single stranded 21?24-nucleotide small noncoding RNAs, and inhibit the expression of their target genes post-transcriptionally (RNA silencing) in a wide range of organisms. The process of miRNA-mediated RNA silencing is involved in diverse biological phenomena including development and cell proliferation, and in diseases such as cancer, but its precise molecular mechanism remains largely unknown.

MiRNA induces target mRNA degradation and/or translational repression by forming a complex with Ago and GW182 family proteins. Hitherto it had been thought that this miRNA-mediated RNA silencing occurred mainly in the cytoplasm. However, Project Research Associate Kenji Nishi, Associate Professor Kumiko Ui-Tei and their colleagues at Department of Biophysics and Biochemistry, Graduate School of Science, the University of Tokyo have revealed the nuclear import machinery of miRNAs. The researchers found that TNRC6A, one of the human GW182 family proteins, is a nuclear- cytoplasmic shuttling protein, and transports miRNAs into the nucleus via its interaction with Ago protein. Furthermore, they also demonstrated that when localized to the nucleus the miRNA-Ago-TNRC6A complex may induce miRNA-mediated RNA silencing, and also other as yet unknown functions, indicating future directions for research in this field.

Press release (Japanese)

Paper

Kenji Nishi, Ai Nishi, Tatsuya Nagasawa, Kumiko Ui-Tei,
“Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus”,
RNA Online Edition: 2012/11/14 (Japan time), doi: 10.1261/rna.034769.112.
Article link

Links

Graduate School of Science

Department of Biophysics and Biochemistry

Ui-Tei Laboratory

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