Transcriptome-wide analysis of TDP-43 binding small RNAs identifies miR-NID1 (miR-8485), a novel miRNA that represses NRXN1 expression.

The Tar DNA-binding protein 43 (TARDBP, TDP-43) regulates RNA processing and miRNA biogenesis and is known to be involved in neurodegeneration. Messenger RNA (mRNA) targets of TDP-43 have recently been systematically identified, but small RNAs (sRNAs) bound by TDP-43 have not been studied in details. Here, we reexamine cross-linking, immunoprecipitation and sequencing (CLIP-seq) data, and identify pre-miRNAs, miRNAs and piRNAs bound by TDP-43 in human and mouse brains. Subsequent analysis of TDP-43 binding miRNAs suggests that target genes are enriched in functions involving synaptic activities. We further identify a novel miRNA (miR-NID1) processed from the intron 5 of human neurexin 1, NRXN1, and show that miR-NID1 represses NRXN1 expression by binding to TDP-43. Our results are in accordance with previously published data indicating TDP-43 through binding of specific miRNAs to play roles in neurodevelopmental activities and neurological disorders and further our understanding of TDP-43 function.