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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3646-3653.
Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2006-01-030015.
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Submitted January 30, 2006
Accepted July 18, 2006
MicroRNAs: regulators of gene expression and cell
differentiation
Ramesh A Shivdasani*
Dana-Farber Cancer Institute, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA
* Corresponding author; email: ramesh_shivdasani{at}dfci.harvard.edu.
The existence and roles of a class of abundant
regulatory RNA molecules have recently come into sharp
focus. MicroRNAs (miRNAs) are small (~22 bases), non-
protein-coding RNAs that recognize target sequences of
imperfect complementarity in cognate mRNAs and either
destabilize them or inhibit protein translation.
Although mechanisms of miRNA biogenesis have been
elucidated in some detail, there is limited appreciation
of their biological functions. Reported examples
typically focus on miRNA regulation of a single tissue-
restricted transcript, often one encoding a
transcription factor, that controls a specific aspect of
development, cell differentiation or physiology.
However, computational algorithms predict up to hundreds
of putative targets for individual miRNAs, single
transcripts may be regulated by multiple miRNAs, and
miRNAs may either eliminate target gene expression or
serve to fine-tune transcript and protein levels.
Theoretical considerations and early experimental
results hence suggest diverse roles for miRNAs as a
class. One appealing possibility, that miRNAs eliminate
low-level expression of unwanted genes and hence refine
unilineage gene expression, may be especially amenable
to evaluation in models of hematopoiesis. This review
summarizes current understanding of miRNA mechanisms,
outlines some of the important outstanding questions,
and describes studies that attempt to define miRNA
functions in hematopoiesis.
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