| First Author | Kawahara Y | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 9 | Pages | 3347-52 |
| PubMed ID | 22323604 | Mgi Jnum | J:181992 |
| Mgi Id | MGI:5314554 | Doi | 10.1073/pnas.1112427109 |
| Citation | Kawahara Y, et al. (2012) TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc Natl Acad Sci U S A 109(9):3347-52 |
| abstractText | Although aberrant microRNA (miRNA) expression is linked to human diseases including cancer, the mechanisms that regulate the expression of each individual miRNA remain largely unknown. TAR DNA-binding protein-43 (TDP-43) is homologous to the heterogeneous nuclear ribonucleoproteins (hnRNPs), which are involved in RNA processing, and its abnormal cellular distribution is a key feature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), two neurodegenerative diseases. Here, we show that TDP-43 facilitates the production of a subset of precursor miRNAs (pre-miRNAs) by both interacting with the nuclear Drosha complex and binding directly to the relevant primary miRNAs (pri-miRNAs). Furthermore, cytoplasmic TDP-43, which interacts with the Dicer complex, promotes the processing of some of these pre-miRNAs via binding to their terminal loops. Finally, we show that involvement of TDP-43 in miRNA biogenesis is indispensable for neuronal outgrowth. These results support a previously uncharacterized role for TDP-43 in posttranscriptional regulation of miRNA expression in both the nucleus and the cytoplasm. |
