Lin-4 microRNA precursor

{{Infobox rfam

| Name = lin-4 microRNA precursor

| image = RF00052.jpg

| width =

| caption = Predicted secondary structure and sequence conservation of lin-4

| Symbol = lin-4

| AltSymbols =

| Rfam = RF00052

| miRBase = MI0000002

| miRBase_family = MIPF0000303

| RNA_type = Gene; miRNA

| Tax_domain = Eukaryota

| GO = {{GO|0035195}} {{GO|0035068}}

| SO = {{SO|0001244}}

| CAS_number =

| EntrezGene =

| HGNCid =

| OMIM =

| PDB =

| RefSeq =

| Chromosome =

| Arm =

| Band =

| LocusSupplementaryData =

}}

In molecular biology lin-4 is a microRNA (miRNA) that was identified from a study of developmental timing in the nematode Caenorhabditis elegans.{{cite journal |vauthors=Lee RC, Feinbaum RL, Ambros V | title = The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.| journal = Cell | year = 1993 | volume = 75 | issue = 5 | pages = 843–854 | doi = 10.1016/0092-8674(93)90529-Y| pmid=8252621| doi-access = free }}{{cite journal | last = Rougvie | first = AE | year = 2001 | title = Control of developmental timing in animals | journal = Nat Rev Genet | volume = 2 | pages = 690–701 | pmid = 11533718 | doi = 10.1038/35088566 | issue = 9}} It was the first to be discovered of the miRNAs, a class of non-coding RNAs involved in gene regulation.{{cite journal | last = Ambros | first = V | year = 2001 | title = microRNAs: tiny regulators with great potential | journal = Cell | volume = 107 | pages = 823–826 | pmid = 11779458 | doi = 10.1016/S0092-8674(01)00616-X | issue = 7| doi-access = free }} miRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a 21 nucleotide product. The extents of the hairpin precursors are not generally known and are estimated based on hairpin prediction. The products are thought to have regulatory roles through complete or partial complementarity to mRNA. The lin-4 gene has been found to lie within a 4.11kb intron of a separate host gene lho-1 (see also [http://www.wormbook.org/wli/wbg15.2p49/]).

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.{{cite journal|vauthors=Balasubramanian C, Ojha RP, Maiti S, Desideri A | title=Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by molecular dynamics simulations. | journal=J Phys Chem B | year= 2010 | volume= 114 | issue= 49 | pages= 16443–9 | pmid=21090710 | doi=10.1021/jp104193r | url=https://pubmed.ncbi.nlm.nih.gov/21090710 }} 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 regards to their modification of development.{{cite journal|vauthors=Boehm M, Slack F | title=A developmental timing microRNA and its target regulate life span in C. elegans. | journal=Science | year= 2005 | volume= 310 | issue= 5756 | pages= 1954–7 | pmid=16373574 | doi=10.1126/science.1115596 | url=https://pubmed.ncbi.nlm.nih.gov/16373574 | doi-access= }}

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{{cite journal|vauthors=Ambros V, Horvitz HR | title=The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. | journal=Genes Dev | year= 1987 | volume= 1 | issue= 4 | pages= 398–414 | pmid=3678829 | doi= 10.1101/gad.1.4.398| doi-access= free }}{{cite journal| author=Ambros V| title=A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. | journal=Cell | year= 1989 | volume= 57 | issue= 1 | pages= 49–57 | pmid=2702689 | doi= 10.1016/0092-8674(89)90171-2| url=https://pubmed.ncbi.nlm.nih.gov/2702689 }} and represses accumulation of the LIN-14 protein.{{cite journal|vauthors=Olsen PH, Ambros V | title=The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. | journal=Dev Biol | year= 1999 | volume= 216 | issue= 2 | pages= 671–80 | pmid=10642801 | doi=10.1006/dbio.1999.9523 | doi-access=free }} It also targets lin-28 and reduces its protein expression through translational inhibition.{{cite journal |vauthors=Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, etal | title=Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. | journal=Cell | year= 2005 | volume= 122 | issue= 4 | pages= 553–63 | pmid=16122423 | doi=10.1016/j.cell.2005.07.031 | doi-access=free }} The base pairing in place between lin-4 and the target In question is discontinuous, consisting of two short helices.{{cite journal| author=Ambros V| title=microRNAs: tiny regulators with great potential. | journal=Cell | year= 2001 | volume= 107 | issue= 7 | pages= 823–6 | pmid=11779458 | doi= 10.1016/S0092-8674(01)00616-X| doi-access= free }}

References

External links

{{Rfam|id=RF00052|name=lin-4 microRNA precursor}}
[https://archive.today/20121223141415/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_entry.pl?acc=MI0000002 MirBase entry for lin-4]

Category:MicroRNA