Lin-14 Explained
| Protein LIN-14 |
| Organism: | Caenorhabditis elegans |
| Taxid: | 6239 |
| Symbol: | lin-14 |
| Entrezgene: | 181337 |
| Refseqmrna: | NM_077515.5 |
| Refseqprotein: | NP_509916.2 |
| Uniprot: | Q21446 |
| Chromosome: | X |
| Entrezchromosome: | NC_003284.9 |
| Genloc Start: | 11462512 |
| Genloc End: | 11488917 |
LIN-14 is a nuclear protein that plays a crucial role in regulating developmental timing in the nematode worm Caenorhabditis elegans.[1] [2] It functions as a heterochronic gene, controlling the timing of developmental events during larval development. LIN-14 protein levels are high at the beginning of the first larval stage (L1) and then rapidly decline, which is essential for the transition from early to late cell fates. LIN-14 is a BEN domain transcription factor, capable of binding DNA and directly regulating gene expression.[3] The protein's activity is tightly regulated by lin-4, a microRNA which inhibits LIN-14 protein synthesis through complementary base pairing with sequences in the lin-14 mRNA 3' untranslated region.[4]
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.[5] These Lin-4 microRNAs bind to complementary sequences in the 3' untranslated region (UTR) of the Lin-14 mRNA, forming multiple RNA duplexes.[6] This interaction leads to a post-transcriptional regulation of Lin-14 translation, resulting in a decrease over time of LIN-14 protein levels starting in the first larval stage (L1).[7]
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, awarded to Victor Ambros and Gary Ruvkun "...for the discovery of microRNA and its role in post-transcriptional gene regulation."[8] Their work on the lin-4 microRNA and its regulation of the Lin-14 protein dates back to the late 1980s and early 1990s.[9]
Notes and References
- Hong Y, Lee RC, Ambros V . Structure and function analysis of LIN-14, a temporal regulator of postembryonic developmental events in Caenorhabditis elegans . Molecular and Cellular Biology . 20 . 6 . 2285–2295 . March 2000 . 10688674 . 110844 . 10.1128/MCB.20.6.2285-2295.2000 .
- Ambros V . Control of developmental timing in Caenorhabditis elegans . Current Opinion in Genetics & Development . 10 . 4 . 428–433 . August 2000 . 10889059 . 10.1016/s0959-437x(00)00108-8 .
- Greene S, Huang J, Hamilton K, Tong L, Hobert O, Sun H . The heterochronic LIN-14 protein is a BEN domain transcription factor . Current Biology . 33 . 6 . R217–R218 . March 2023 . 36977380 . 10080584 . 10.1016/j.cub.2023.02.016 . 2023CBio...33R.217G .
- Hristova M, Birse D, Hong Y, Ambros V . 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 . Molecular and Cellular Biology . 25 . 24 . 11059–11072 . December 2005 . 16314527. 1316966 . 10.1128/MCB.25.24.11059-11072.2005 .
- Lee RC, Feinbaum RL, Ambros V . The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 . Cell . 75 . 5 . 843–54 . December 1993 . 8252621 . 10.1016/0092-8674(93)90529-y .
- Wightman B, Ha I, Ruvkun G . Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans . Cell . 75 . 5 . 855–62 . December 1993 . 8252622 . 10.1016/0092-8674(93)90530-4 .
- Shi Z, Hayes G, Ruvkun G . Dual regulation of the lin-14 target mRNA by the lin-4 miRNA . PLOS ONE . 8 . 9 . e75475 . 2013 . 24058689 . 3772890 . 10.1371/journal.pone.0075475 . free . 2013PLoSO...875475S .
- Web site: The Nobel Prize in Physiology or Medicine 2024 . 10 October 2024 . The Nobel Foundation .
- Ambros V, Horvitz HR . The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events . Genes & Development . 1 . 4 . 398–414 . June 1987 . 3678829 . 10.1101/gad.1.4.398 . free .
