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lin-4 microRNA precursor
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<h2 id="transcription">Transcription</h2> <p>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 <a href="/facts/Endogenous/DFkSLkRI">endogenous</a> lin-4 primary transcripts upon appearance of the lin-4 mature form.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> lin-4 is found on chromosome II in <i>C. elegans</i> and is complementary to sequences in the <a href="/facts/Three_prime_untranslated_region/wB0oYfKd">3' untranslated region (UTR)</a> of lin-14 mRNA, this complementary transcript containing seven binding sites along with the 9 nucleotide core element CUCAGGGAA. The lin-4:<a href="/facts/Lin-14/gMmUhshw">lin-14</a> 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.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> This lin-4:lin-14 pair have been linked to the <a href="/facts/Insulin-like_growth_factor_1/2n0nPvtD">IGF-1</a> pathway in C. elegans with regards to their modification of development.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p> <h2 id="developmental-influence">Developmental influence</h2> <p>lin-4 acts to dictate the onset of larval stages of developmental events in <i>C. elegans</i>. 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 <a href="/facts/Heterochrony/HHRRnCCH">heterochronic</a> developmental patterns, with loss of structures such as the vulva and adult cuticle.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> lin-4 acts as a negative regulator of lin-14<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> and represses accumulation of the LIN-14 protein.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> It also targets lin-28 and reduces its protein expression through translational inhibition.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> The base pairing in place between lin-4 and the target In question is discontinuous, consisting of two short helices.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p> <h2 id="external-links">External links</h2> <ul><li></li> <li><a href="http://rfam.xfam.org/family?entry=RF00052">Page for lin-4 microRNA precursor</a> at <a href="/facts/Rfam/pl9awpRM">Rfam</a></li> <li><a href="https://archive.today/20121223141415/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_entry.pl?acc=MI0000002">MirBase entry for lin-4</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Lee RC, Feinbaum RL, Ambros V (1993). "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14". Cell. 75 (5): 843–854. doi:10.1016/0092-8674(93)90529-Y. PMID 8252621. <a href="https://doi.org/10.1016%2F0092-8674%2893%2990529-Y" target="_blank">https://doi.org/10.1016%2F0092-8674%2893%2990529-Y</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Rougvie, AE (2001). "Control of developmental timing in animals". Nat Rev Genet. 2 (9): 690–701. doi:10.1038/35088566. PMID 11533718. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Ambros, V (2001). "microRNAs: tiny regulators with great potential". Cell. 107 (7): 823–826. doi:10.1016/S0092-8674(01)00616-X. PMID 11779458. <a href="https://doi.org/10.1016%2FS0092-8674%2801%2900616-X" target="_blank">https://doi.org/10.1016%2FS0092-8674%2801%2900616-X</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Balasubramanian C, Ojha RP, Maiti S, Desideri A (2010). "Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by molecular dynamics simulations". J Phys Chem B. 114 (49): 16443–9. doi:10.1021/jp104193r. PMID 21090710. <a href="https://pubmed.ncbi.nlm.nih.gov/21090710" target="_blank">https://pubmed.ncbi.nlm.nih.gov/21090710</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Balasubramanian C, Ojha RP, Maiti S, Desideri A (2010). "Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by molecular dynamics simulations". J Phys Chem B. 114 (49): 16443–9. doi:10.1021/jp104193r. PMID 21090710. <a href="https://pubmed.ncbi.nlm.nih.gov/21090710" target="_blank">https://pubmed.ncbi.nlm.nih.gov/21090710</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Boehm M, Slack F (2005). "A developmental timing microRNA and its target regulate life span in C. elegans". Science. 310 (5756): 1954–7. doi:10.1126/science.1115596. PMID 16373574. <a href="https://pubmed.ncbi.nlm.nih.gov/16373574" target="_blank">https://pubmed.ncbi.nlm.nih.gov/16373574</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Lee RC, Feinbaum RL, Ambros V (1993). "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14". Cell. 75 (5): 843–854. doi:10.1016/0092-8674(93)90529-Y. PMID 8252621. <a href="https://doi.org/10.1016%2F0092-8674%2893%2990529-Y" target="_blank">https://doi.org/10.1016%2F0092-8674%2893%2990529-Y</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Ambros V, Horvitz HR (1987). "The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events". Genes Dev. 1 (4): 398–414. doi:10.1101/gad.1.4.398. PMID 3678829. <a href="https://doi.org/10.1101%2Fgad.1.4.398" target="_blank">https://doi.org/10.1101%2Fgad.1.4.398</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Ambros V (1989). "A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans". Cell. 57 (1): 49–57. doi:10.1016/0092-8674(89)90171-2. PMID 2702689. <a href="https://pubmed.ncbi.nlm.nih.gov/2702689" target="_blank">https://pubmed.ncbi.nlm.nih.gov/2702689</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Olsen PH, Ambros V (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. 216 (2): 671–80. doi:10.1006/dbio.1999.9523. PMID 10642801. <a href="https://doi.org/10.1006%2Fdbio.1999.9523" target="_blank">https://doi.org/10.1006%2Fdbio.1999.9523</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, et al. (2005). "Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation". Cell. 122 (4): 553–63. doi:10.1016/j.cell.2005.07.031. PMID 16122423. <a href="https://doi.org/10.1016%2Fj.cell.2005.07.031" target="_blank">https://doi.org/10.1016%2Fj.cell.2005.07.031</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Ambros V (2001). "microRNAs: tiny regulators with great potential". Cell. 107 (7): 823–6. doi:10.1016/S0092-8674(01)00616-X. PMID 11779458. <a href="https://doi.org/10.1016%2FS0092-8674%2801%2900616-X" target="_blank">https://doi.org/10.1016%2FS0092-8674%2801%2900616-X</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> </ol>