Lin-4 microRNA precursor

Transcription

lin-4 is transcribed from autonomous miRNA promoters and is developmentally regulated, with lin-4 miRNA accumulation occurring at the L2 stage of post-embryonic development. Additional to this is the up-regulation of endogenous lin-4 primary transcripts upon appearance of the lin-4 mature form. lin-4 is found on chromosome II in C. elegans and is complementary to sequences in the 3' untranslated region (UTR) of lin-14 mRNA, this complementary transcript containing seven binding sites along with the 9 nucleotide core element CUCAGGGAA. The lin-4:lin-14 duplex is seen to take up an unusual kinked structure, caused by induced changes in the groove dimension and base stacking due to the mismatched base pairs. This lin-4:lin-14 pair have been linked to the IGF-1 pathway in C. elegans with regard to their modification of development.

Developmental influence

lin-4 acts to dictate the onset of larval stages of developmental events in C. elegans. lin-4 loss of function (lf) mutations see a resultant retardation of developmental fates, from their initially early to instead later larval stages. Consequences include heterochronic developmental patterns, with loss of structures such as the vulva and adult cuticle. lin-4 acts as a negative regulator of lin-14 and represses accumulation of the LIN-14 protein. It also targets lin-28 and reduces its protein expression through translational inhibition. The base pairing in place between lin-4 and the target In question is discontinuous, consisting of two short helices.

References

References

1. (1993). "The C. elegans heterochronic gene ''lin-4'' encodes small RNAs with antisense complementarity to ''lin-14''.". Cell.
2. Rougvie, AE. (2001). "Control of developmental timing in animals". Nat Rev Genet.
3. Ambros, V. (2001). "microRNAs: tiny regulators with great potential". Cell.
4. (2010). "Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by molecular dynamics simulations.". J Phys Chem B.
5. (2005). "A developmental timing microRNA and its target regulate life span in C. elegans.". Science.
6. (1987). "The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events.". Genes Dev.
7. Ambros V. (1989). "A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans.". Cell.
8. (1999). "The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation.". Dev Biol.
9. (2005). "Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation.". Cell.
10. Ambros V. (2001). "microRNAs: tiny regulators with great potential.". Cell.