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Leptin-Responsive MiR-4443 Is a Small Regulatory RNA Independent of the Canonic MicroRNA Biogenesis Pathway

by Ari Meerson 1,2
1
MIGAL—Galilee Research Institute, POB 831, Kiryat Shmona 1101602, Israel
2
Faculty of Sciences, Tel-Hai Academic College, Upper Galilee 1220800, Israel
Biomolecules 2020, 10(2), 293; https://doi.org/10.3390/biom10020293 (registering DOI)
Received: 31 December 2019 / Revised: 10 February 2020 / Accepted: 10 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue Leptin and Beyond: Actors in Cancer)
The human small RNA miR-4443 is functionally involved in several types of cancer and in the biology of the immune system, downstream of insulin and leptin signaling. Next generation sequencing evidence and structural prediction suggest that miR-4443 is not produced via the canonical Drosha–Exportin 5–Dicer pathway of microRNA biogenesis. We tested this hypothesis by using qRT-PCR to measure miR-4443 and other microRNA levels in HCT-116 cells with Drosha, Exportin 5, and Dicer knockouts, as well as in the parental cell line. Neither of the knockouts decreased miR-4443 levels, while the levels of canonical microRNAs (miR-21 and let-7f-5p) were dramatically reduced. Previously published Ago2-RIP-Seq data suggest a limited incorporation of miR-4443 into RISC, in agreement with the functional studies. The miR-4443 locus shows conservation in primates but not in other mammals, while its seed region appears in additional microRNAs. Our results suggest that miR-4443 is a Drosha, Exportin 5, and Dicer-independent, non-canonical small RNA produced by a yet unknown biogenesis pathway.
Keywords: noncoding RNA; microRNA; biogenesis; Drosha; Dicer; Exportin; microprocessor; non-canonical; leptin; insulin noncoding RNA; microRNA; biogenesis; Drosha; Dicer; Exportin; microprocessor; non-canonical; leptin; insulin
MDPI and ACS Style

Meerson, A. Leptin-Responsive MiR-4443 Is a Small Regulatory RNA Independent of the Canonic MicroRNA Biogenesis Pathway. Biomolecules 2020, 10, 293.

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