Biology Reference
In-Depth Information
worms that are deficient in lin-14.
42
While most genes identified from
mutagenesis screens encode proteins, lin-4 encodes a 22-nucleotide non-
coding RNA with partial complementarity to evolutionarily conserved
sites located in the 3
UTR) of the lin-14 gene,
6,43
which encodes a nuclear protein involved in the L1-to-L2 transition of
larval development. The discovery of lin-4 and its target-specific transla-
tional inhibition pointed to a new mechanism of gene regulation during
development, yet until the discovery of the let-7 miRNA this mechanism
was thought to be specific to worms. The let-7 miRNA also encodes a
temporally regulated 21-nucleotide small RNA, which controls the
developmental transition from the last larval stage (L4) to the adult
stage.
1
Similar to lin-4, let-7 has partial complementarity to its targets
(among which are lin-41 and hbl-1
44,45
), whose translation it inhibits.
Both let-7 and its target lin-41 are evolutionarily conserved throughout
metazoans, with homologs that were detected in mollusks, sea urchins,
flies, mice, and humans.
2
This degree of conservation strongly pointed to
a general role of small RNAs in developmental regulation. Orthologs of
lin-4 were also later identified in flies and mammals.
4,46
Many subsequent
studies contributed to the catalog of 5234 mature miRNA forms
(564 from human) that are currently present in the miRBase repository.
47
While initially the focus was on identification of deeply conserved
miRNAs,
48
it has recently been proposed that many miRNAs of recent
evolutionary origin exist,
24
although, at least in this particular study, the
clustered miRNAs expressed in the placenta share intriguing sequence
similarities with more deeply conserved miRNAs.
miRNAs have also been found in the genomes of several DNA
viruses, with the Epstein-Barr virus (EBV) being the first found to
encode miRNAs.
5
Computational and experimental analysis further
revealed miRNAs in other
Herpesviridae
such as the
′
untranslated region (3
′
γ
-herpesvirus
Kaposi's sarcoma-associated virus (KSHV), the
γ
-herpesvirus murine
herpesvirus 68 (MHV68), and the
-herpesvirus human cytomegalovirus
(HCMV).
49-52
miRNA gene prediction provides no evidence that other
herpesviruses, like the
β
α
-herpesvirus HHV3 (varicella-zoster virus) or
β
-herpesviruses HHV6 and HHV7, encode miRNAs.
49
Besides
Herpesviridae
, miRNAs have been found in the genomes of other viruses,
particularly polyomaviruses. Computational prediction first indicated the
