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Caenorhabditis elegans is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek caeno- (recent), rhabditis (rod-like) and Latin elegans (elegant). In 1900, Maupas initially named it Rhabditides elegans. Osche placed it in the subgenus Caenorhabditis in 1952, and in 1955, Dougherty raised Caenorhabditis to the status of genus.
Micro ribonucleic acid are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in messenger RNA (mRNA) molecules, then silence said mRNA molecules by one or more of the following processes:
Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM is an American biologist whose research on the nematode worm Caenorhabditis elegans was awarded the 2002 Nobel Prize in Physiology or Medicine, together with Sydney Brenner and John E. Sulston, whose "seminal discoveries concerning the genetic regulation of organ development and programmed cell death" were "important for medical research and have shed new light on the pathogenesis of many diseases".
The DAF-2 gene encodes for the insulin-like growth factor 1 (IGF-1) receptor in the worm Caenorhabditis elegans. DAF-2 is part of the first metabolic pathway discovered to regulate the rate of aging. DAF-2 is also known to regulate reproductive development, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and resistance to bacterial pathogens. Mutations in DAF-2 and also Age-1 have been shown by Cynthia Kenyon to double the lifespan of the worms. In a 2007 episode of WNYC’s Radiolab, Kenyon called DAF-2 "the grim reaper gene.”
Small temporal RNA regulates gene expression during roundworm development by preventing the mRNAs they bind from being translated. In contrast to siRNA, stRNAs downregulate expression of target RNAs after translation initiation without affecting mRNA stability. Nowadays, stRNAs are better known as miRNAs.
The Let-7 microRNA precursor was identified from a study of developmental timing in C. elegans, and was later shown to be part of a much larger class of non-coding RNAs termed microRNAs. miR-98 microRNA precursor from human is a let-7 family member. Let-7 miRNAs have now been predicted or experimentally confirmed in a wide range of species (MIPF0000002). miRNAs are initially transcribed in long transcripts called primary miRNAs (pri-miRNAs), which are processed in the nucleus by Drosha and Pasha to hairpin structures of about 70 nucleotide. These precursors (pre-miRNAs) are exported to the cytoplasm by exportin5, where they are subsequently processed by the enzyme Dicer to a ~22 nucleotide mature miRNA. The involvement of Dicer in miRNA processing demonstrates a relationship with the phenomenon of RNA interference.
In molecular biology lin-4 is a microRNA (miRNA) that was identified from a study of developmental timing in the nematode Caenorhabditis elegans. It was the first to be discovered of the miRNAs, a class of non-coding RNAs involved in gene regulation. 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.
The mir-10 microRNA precursor is a short non-coding RNA gene involved in gene regulation. It is part of an RNA gene family which contains mir-10, mir-51, mir-57, mir-99 and mir-100. mir-10, mir-99 and mir-100 have now been predicted or experimentally confirmed in a wide range of species. miR-51 and miR-57 have currently only been identified in the nematode Caenorhabditis elegans.
The miR-1 microRNA precursor is a small micro RNA that regulates its target protein's expression in the cell. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give products at ~22 nucleotides. In this case the mature sequence comes from the 3' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In humans there are two distinct microRNAs that share an identical mature sequence, and these are called miR-1-1 and miR-1-2.
Sir David Charles Baulcombe is a British plant scientist and geneticist. As of October 2024 he was Head of Group, Gene Expression, in the Department of Plant Sciences at the University of Cambridge, and the Edward Penley Abraham Royal Society Research Professor and Regius Professor of Botany Emeritus at Cambridge. He held the Regius botany chair in that department from 2007 to 2020.
Lin-28 homolog A is a protein that in humans is encoded by the LIN28 gene.
Victor R. Ambros is an American developmental biologist and Nobel Laureate who discovered the first known microRNA (miRNA). He is a professor at the University of Massachusetts Medical School. He completed both his undergraduate and doctoral studies at the Massachusetts Institute of Technology. Ambros received the Nobel Prize in Physiology or Medicine in 2024 for his research on microRNA.
Gary Bruce Ruvkun is an American molecular biologist and Nobel laureate at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston.
DAF-16 is the sole ortholog of the FOXO family of transcription factors in the nematode Caenorhabditis elegans. It is responsible for activating genes involved in longevity, lipogenesis, heat shock survival and oxidative stress responses. It also protects C.elegans during food deprivation, causing it to transform into a hibernation - like state, known as a Dauer. DAF-16 is notable for being the primary transcription factor required for the profound lifespan extension observed upon mutation of the insulin-like receptor DAF-2. The gene has played a large role in research into longevity and the insulin signalling pathway as it is located in C. elegans, a successful ageing model organism.
mir-48 microRNA is a microRNA which is found in nematodes, in which it controls developmental timing. It acts in the heterochronic pathway, where it controls the timing of cell fate decisions in the vulva and hypodermis during larval development.
MicroRNA sequencing (miRNA-seq), a type of RNA-Seq, is the use of next-generation sequencing or massively parallel high-throughput DNA sequencing to sequence microRNAs, also called miRNAs. miRNA-seq differs from other forms of RNA-seq in that input material is often enriched for small RNAs. miRNA-seq allows researchers to examine tissue-specific expression patterns, disease associations, and isoforms of miRNAs, and to discover previously uncharacterized miRNAs. Evidence that dysregulated miRNAs play a role in diseases such as cancer has positioned miRNA-seq to potentially become an important tool in the future for diagnostics and prognostics as costs continue to decrease. Like other miRNA profiling technologies, miRNA-Seq has both advantages and disadvantages.
In molecular biology mir-84 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
In molecular biology mir-241 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
NamiRNAs are a type of miRNAs present in the nucleus, which can activate gene expression by binding to the enhancer, and therefore were named nuclear activating miRNAs (NamiRNAs), such as miR-24-1 and miR-26. These miRNAs loci are enriched with epigenetic markers that display enhancer activity like histone H3K27ac, P300/CBP, and DNaseI high-sensitivity loci. These NamiRNAs are able to activate the related enhancers and co-work with them to up-regulate the expression of neighboring genes. NamiRNAs are able to promote global gene transcription by binding their targeted enhancers in whole genome level.
Rosalind 'Candy' Lee is a biomedical scientist, best known for her breakthrough paper on the discovery of microRNA which was published in 1993. In 2002, Lee was joint receipient of the Newcomb Cleveland Prize, for the best paper published in the journal Science that year. In 2024, Lee's 1993 paper was cited as the seminal discovery for which the Nobel Prize in physiology or medicine was awarded that year, to co-author Victor Ambros.
References
- ↑ Hong Y, Lee RC, Ambros V (March 2000). "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. doi:10.1128/MCB.20.6.2285-2295.2000. PMC 110844 . PMID 10688674.
- 1 2 3 Ambros V (August 2000). "Control of developmental timing in Caenorhabditis elegans". Current Opinion in Genetics & Development. 10 (4): 428–433. doi:10.1016/s0959-437x(00)00108-8. PMID 10889059.
- ↑ Greene S, Huang J, Hamilton K, Tong L, Hobert O, Sun H (March 2023). "The heterochronic LIN-14 protein is a BEN domain transcription factor". Current Biology. 33 (6): R217–R218. Bibcode:2023CBio...33R.217G. doi:10.1016/j.cub.2023.02.016. PMC 10080584 . PMID 36977380.
- ↑ Hristova M, Birse D, Hong Y, Ambros V (December 2005). "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. doi:10.1128/MCB.25.24.11059-11072.2005. PMC 1316966 . PMID 16314527.
- 1 2 Lee RC, Feinbaum RL, Ambros V (December 1993). "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14". Cell. 75 (5): 843–54. doi:10.1016/0092-8674(93)90529-y. PMID 8252621.
- 1 2 Wightman B, Ha I, Ruvkun G (December 1993). "Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans". Cell. 75 (5): 855–62. doi:10.1016/0092-8674(93)90530-4. PMID 8252622.
- ↑ Shi Z, Hayes G, Ruvkun G (2013). "Dual regulation of the lin-14 target mRNA by the lin-4 miRNA". PLOS ONE. 8 (9): e75475. Bibcode:2013PLoSO...875475S. doi: 10.1371/journal.pone.0075475 . PMC 3772890 . PMID 24058689.
- ↑ "The Nobel Prize in Physiology or Medicine 2024". The Nobel Foundation. 10 October 2024.
- ↑ Ambros V, Horvitz HR (June 1987). "The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events". Genes & Development. 1 (4): 398–414. doi: 10.1101/gad.1.4.398 . PMID 3678829.
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