Research in Recognition and Functional Categorization of miRNAs
|
A group of small RNA molecules, distinct from but related
to siRNAs, have been identified in a variety of organisms.
These small RNAs, called microRNAs (miRNAs), are transcribed
as parts of longer RNA molecules that can be as long as
1000 nt. The RNAs are processed in the nucleus into hairpin
RNAs of 70-100 nt by the dsRNA-specific ribonuclease Drosha.
The hairpin RNAs are transported to the cytoplasm via
a transportin-5 dependent mechanism where they are digested
by a second, double-strand specific ribonuclease called
Dicer. The resulting 19-23 mer miRNA is bound by a complex
that is similar to the RNA-Induced Silencing Complex (RISC)
that participates in RNA interference (RNAi). In animals,
the complex-bound, single-stranded miRNA binds specific
mRNAs through sequences that are significantly, though
not completely, complementary to the mRNA. By a mechanism
that is not fully characterized— but which apparently
does not involve mRNA degradation as in RNAi - the bound
mRNA remains untranslated, resulting in reduced expression
of the corresponding gene.
The function of most miRNAs is not known. A number of miRNAs, however, seem to be involved in gene regulation. Some of these miRNAs, including lin-4 and let-7, inhibit protein synthesis by binding to partially complementary 3' untranslated regions (3' UTRs) of target mRNAs. Others, including the Scarecrow miRNA found in plants, function like siRNA and bind to perfectly complementary mRNA sequences to destroy the target transcript (1). Some miRNAs, such as lin-4, let-7, mir-14, mir-23, and bantam, have been shown to play critical roles in cell differentiation and tissue development (2,3). Others are believed to have similarly important roles because of their differential spatial and temporal expression patterns. There is speculation that miRNAs may represent a new aspect of gene regulation, and there is intense interest among researchers around the world in their targets and mechanism of action. Published reports indicate that the expression levels of miRNAs vary between tissues and developmental stages, and that several miRNAs appear to be down-regulated in patients with chronic lymphocytic leukemia, colonic adenocarcinoma, and Burkitt's lymphoma. Hence, it is of increasing interest and biomedical importance to obtain expression data for miRNA genes using chip technology. Various companies have made efforts towards this goal and it would be vary enlightening when more of such information is made available to the academic community. Ongoing Projects: 1. Mature miRNA cut site prediction using Hidden Markov Models |
