# Lin-14
> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Lin-14
> Markdown URL: https://mediated.wiki/source/Lin-14.md
> Source: https://en.wikipedia.org/wiki/Lin-14
> Source revision: 1313986046
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)
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{{Infobox nonhuman protein
| Name = Protein LIN-14
| image =
| width =
| caption =
| Organism = Caenorhabditis elegans
| TaxID = 6239
| Symbol = lin-14
| AltSymbols =
| EntrezGene = 181337
| HomoloGene =
| PDB =
| RefSeqmRNA = NM_077515.5
| RefSeqProtein = NP_509916.2
| UniProt = Q21446
| ECnumber =
| Chromosome = X
| EntrezChromosome = NC_003284.9
| GenLoc_start = 11462512
| GenLoc_end = 11488917
}}
'''LIN-14''' is a [nuclear protein](/source/nuclear_protein) that plays a crucial role in regulating [developmental](/source/developmental_biology) timing in the [nematode](/source/nematode) worm ''[Caenorhabditis elegans](/source/Caenorhabditis_elegans)''.[{{cite journal | vauthors = Hong Y, Lee RC, Ambros V | title = Structure and function analysis of LIN-14, a temporal regulator of postembryonic developmental events in Caenorhabditis elegans | journal = Molecular and Cellular Biology | volume = 20 | issue = 6 | pages = 2285–2295 | date = March 2000 | pmid = 10688674 | pmc = 110844 | doi = 10.1128/MCB.20.6.2285-2295.2000 }}][{{cite journal | vauthors = Ambros V | title = Control of developmental timing in Caenorhabditis elegans | journal = Current Opinion in Genetics & Development | volume = 10 | issue = 4 | pages = 428–433 | date = August 2000 | pmid = 10889059 | doi = 10.1016/s0959-437x(00)00108-8 }}] It functions as a heterochronic gene, controlling the timing of developmental events during [larval](/source/larval) development.[{{cite journal | vauthors = Greene S, Huang J, Hamilton K, Tong L, Hobert O, Sun H | title = The heterochronic LIN-14 protein is a BEN domain transcription factor | journal = Current Biology | volume = 33 | issue = 6 | pages = R217–R218 | date = March 2023 | pmid = 36977380 | pmc = 10080584 | doi = 10.1016/j.cub.2023.02.016 | bibcode = 2023CBio...33R.217G }}] The protein's activity is tightly regulated by [lin-4](/source/lin-4_microRNA_precursor), a [microRNA](/source/microRNA) which inhibits LIN-14 [protein synthesis](/source/protein_synthesis) through complementary [base pairing](/source/base_pairing) with sequences in the lin-14 mRNA [3' untranslated region](/source/3'_untranslated_region).[{{cite journal | vauthors = Hristova M, Birse D, Hong Y, Ambros V | title = The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/insulin-like growth factor gene ins-33 by direct DNA binding | journal = Molecular and Cellular Biology | volume = 25 | issue = 24 | pages = 11059–11072 | date = December 2005 | pmid = 16314527| pmc = 1316966 | doi = 10.1128/MCB.25.24.11059-11072.2005 }}]
== Regulation ==
The expression of the Lin-14 gene in ''Caenorhabditis elegans'' is tightly regulated by the Lin-4 gene through a microRNA-mediated mechanism. Lin-4 produces small RNAs that act as negative regulators of Lin-14 protein synthesis.[{{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 | volume = 75 | issue = 5 | pages = 843–54 | date = December 1993 | pmid = 8252621 | doi = 10.1016/0092-8674(93)90529-y | doi-access = free }}] These Lin-4 microRNAs bind to complementary sequences in the 3' untranslated region (UTR) of the Lin-14 mRNA, forming multiple RNA duplexes.[{{cite journal | vauthors = Wightman B, Ha I, Ruvkun G | title = Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans | journal = Cell | volume = 75 | issue = 5 | pages = 855–62 | date = December 1993 | pmid = 8252622 | doi = 10.1016/0092-8674(93)90530-4 }}] This interaction leads to a [post-transcriptional regulation](/source/post-transcriptional_regulation) of Lin-14 [translation](/source/translation_(biology)), resulting in a decrease over time of LIN-14 protein levels starting in the first larval stage (L1).[{{cite journal | vauthors = Shi Z, Hayes G, Ruvkun G | title = Dual regulation of the lin-14 target mRNA by the lin-4 miRNA | journal = PLOS ONE | volume = 8 | issue = 9 | article-number = e75475 | date = 2013 | pmid = 24058689 | pmc = 3772890 | doi = 10.1371/journal.pone.0075475 | doi-access = free | bibcode = 2013PLoSO...875475S }}]
==Nobel Prize==
This work on microRNA-mediated gene regulation, including the discovery of the Lin-4/Lin-14 regulatory mechanism, was recognized with the 2024 [Nobel Prize in Physiology or Medicine](/source/Nobel_Prize_in_Physiology_or_Medicine), awarded to [Victor Ambros](/source/Victor_Ambros) and [Gary Ruvkun](/source/Gary_Ruvkun) "...for the discovery of microRNA and its role in post-transcriptional gene regulation."[{{cite web | title = The Nobel Prize in Physiology or Medicine 2024 | date = 10 October 2024 | url = https://www.nobelprize.org/prizes/medicine/2024/press-release/ | work = The Nobel Foundation }}] Their work on the ''lin-4'' microRNA and its regulation of the ''Lin-14'' protein dates back to the late 1980s and early 1990s.[{{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 & Development | volume = 1 | issue = 4 | pages = 398–414 | date = June 1987 | pmid = 3678829 | doi = 10.1101/gad.1.4.398 | doi-access = free }}]