NEUROGENESIS AND DISEASE (L CAI, SECTION EDITOR)
New Insights: MicroRNA Function in CNS Development
and Psychiatric Diseases
Published online: 22 February 2018
Springer International Publishing AG, part of Springer Nature 2018
Purpose of Review Here, we concisely review microRNA (miRNA)-related research publications on the central nervous system
(CNS) development (focusing on the forebrain and the cerebellum) and related psychiatric diseases over the past 3 years. We
intend to summarize the new insights from these publications and, at the same time, provide personal views on some of the
important mechanistic questions in the field.
Recent Findings MiRNAs, a type of small non-coding RNA molecules, have emerged as essential players in many biological
processes. During CNS development, miRNAs have also been shown to exert their posttranscriptional regulation in numerous
developmental events acting from master regulators to fine tuners of gene expression. While a single miRNA miR-980 regulates
neuronal excitability and leads to alterations in behaviors associated with memory, sometimes multiple miRNAs have to
functionally converge to induce one developmental process. Recent findings identified novel target genes for selected
miRNAs during distinct developmental processes, and highlighted their important functions in several signaling pathways.
Meanwhile, abnormal function of miRNAs during CNS development could lead to psychiatric diseases later on in life.
Indeed, genomic variants, microdeletion, and microduplication could directly or indirectly involve miRNAs in the onset of these
Summary Over the years, substantial research discoveries have been made to uncover molecular mechanisms of miRNA action,
especially in the CNS, during normal development and under disease conditions. Thorough understanding of miRNAs function during
these biological processes will facilitate future therapeutic interventions with this small, chemically synthesizable RNA molecules.
Keywords Dicer (Dicer1)
MRS target gene
MicroRNAs (miRNAs) are a class of small non-coding RNAs
that regulate gene expression post-transcriptionally. By
binding to the 3′-untranslated region (3′-UTR) of their target
mRNAs through imperfect base pairing, miRNAs exert their
function by either degrading the targets or inhibiting their
translation [1–3] with exceptions [4–7]. The canonical path-
way for miRNA biogenesis is that miRNAs are first tran-
scribed from the genome as primary miRNAs (pri-
miRNAs), cleaved by Drosha and DGCR8 to form precursor
miRNAs (pre-miRNAs) in the nucleus, and then exported by
Exportin 5 to the cytoplasm where they are further cleaved by
Dicer to generate mature miRNAs. Dicer is an RNase III en-
zyme and indispensable to producing most mature miRNAs,
and therefore, Dicer knockout mice have been widely used as
loss-of-function models to study miRNA functions [8, 9].
Important to note though, there is also a non-canonical path-
way for miRNA biogenesis, which is Dicer-independent .
For example, certain mature miRNAs can be processed from
Ago2 activity alone without the involvement of Dicer.
Qian Liu and Lu Zhang contributed equally to this work.
This article is part of the Topical Collection on Neurogenesis and Disease
* Hedong Li
Key Laboratory of Birth Defects and Related Diseases of Women and
Children, Ministry of Education, West China Second University
Hospital, Sichuan University, Chengdu 610041, People’s Republic of
Sichuan Baili Pharmaceutical Co., Ltd, High-tech International
Plaza, High-tech Zone, Chengdu 610000, People’sRepublicof
Department of Biology, Huck Institutes of Life Sciences, The
Pennsylvania State University, University Park, PA 16802, USA
Current Pharmacology Reports (2018) 4:132–144