miRNA biogenesis and inherited disorders: clinico-molecular insights

Dylan Pelletier; Barbara Rivera; Marc R Fabian; William D Foulkes

doi:10.1016/j.tig.2023.01.009

miRNA biogenesis and inherited disorders: clinico-molecular insights

Trends Genet. 2023 May;39(5):401-414. doi: 10.1016/j.tig.2023.01.009. Epub 2023 Feb 28.

Authors

Dylan Pelletier¹, Barbara Rivera², Marc R Fabian³, William D Foulkes⁴

Affiliations

¹ Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada; Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
² Molecular Mechanisms and Experimental Therapy in Oncology Program - Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
³ Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada; Division of Experimental Medicine, McGill University, Montreal, QC, Canada; Department of Biochemistry, McGill University, Montreal, QC, Canada.
⁴ Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada; Cancer Research Program, Research Institute of the McGill University Health Center, Montreal, QC, Canada. Electronic address: william.foulkes@mcgill.ca.

PMID: 36863945
DOI: 10.1016/j.tig.2023.01.009

Abstract

MicroRNAs (miRNAs) play vital roles in the regulation of gene expression, a process known as miRNA-induced gene silencing. The human genome codes for many miRNAs, and their biogenesis relies on a handful of genes, including DROSHA, DGCR8, DICER1, and AGO1/2. Germline pathogenic variants (GPVs) in these genes cause at least three distinct genetic syndromes, with clinical manifestations that range from hyperplastic/neoplastic entities to neurodevelopmental disorders (NDDs). Over the past decade, DICER1 GPVs have been shown to lead to tumor predisposition. Moreover, recent findings have provided insight into the clinical consequences arising from GPVs in DGCR8, AGO1, and AGO2. Here we provide a timely update with respect to how GPVs in miRNA biogenesis genes alter miRNA biology and ultimately lead to their clinical manifestations.

Keywords: AGO1/2 syndrome; DGCR8 syndrome; DICER1 syndrome; cancer predisposition; miRNA biogenesis; neurodevelopmental disorder.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

DEAD-box RNA Helicases / genetics
DEAD-box RNA Helicases / metabolism
Genome, Human
Genotype
Humans
MicroRNAs* / genetics
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism
Ribonuclease III / genetics
Ribonuclease III / metabolism

Substances

MicroRNAs
RNA-Binding Proteins
Ribonuclease III
DICER1 protein, human
DEAD-box RNA Helicases