Lin-4 microRNA precursor

Last updated
lin-4 microRNA precursor
RF00052.jpg
Predicted secondary structure and sequence conservation of lin-4
Identifiers
Symbollin-4
Rfam RF00052
miRBase MI0000002
miRBase family MIPF0000303
Other data
RNA type Gene; miRNA
Domain(s) Eukaryota
GO GO:0035195 GO:0035068
SO SO:0001244
PDB structures PDBe

In molecular biology lin-4 is a microRNA (miRNA) that was identified from a study of developmental timing in the nematode Caenorhabditis elegans . [1] [2] It was the first to be discovered of the miRNAs, a class of non-coding RNAs involved in gene regulation. [3] 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 (see also ).

Contents

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. [4] 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. [4] This lin-4:lin-14 pair have been linked to the IGF-1 pathway in C. elegans with regards to their modification of development. [5]

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. [1] lin-4 acts as a negative regulator of lin-14 [6] [7] and represses accumulation of the LIN-14 protein. [8] It also targets lin-28 and reduces its protein expression through translational inhibition. [9] The base pairing in place between lin-4 and the target In question is discontinuous, consisting of two short helices. [10]

Related Research Articles

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mir-156 microRNA precursor

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<span class="mw-page-title-main">LIN28</span>

Lin-28 homolog A is a protein that in humans is encoded by the LIN28 gene.

<span class="mw-page-title-main">Victor Ambros</span> American developmental biologist (born 1953)

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Gary Bruce Ruvkun is an American molecular biologist at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston. Ruvkun discovered the mechanism by which lin-4, the first microRNA (miRNA) discovered by Victor Ambros, regulates the translation of target messenger RNAs via imperfect base-pairing to those targets, and discovered the second miRNA, let-7, and that it is conserved across animal phylogeny, including in humans. These miRNA discoveries revealed a new world of RNA regulation at an unprecedented small size scale, and the mechanism of that regulation. Ruvkun also discovered many features of insulin-like signaling in the regulation of aging and metabolism. He was elected a Member of the American Philosophical Society in 2019.

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miR-150 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.

miR-191

miR-191 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.

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miR-296

miR-296 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.

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.

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.

References

  1. 1 2 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.
  2. ↑ Rougvie, AE (2001). "Control of developmental timing in animals". Nat Rev Genet. 2 (9): 690–701. doi:10.1038/35088566. PMID   11533718.
  3. ↑ Ambros, V (2001). "microRNAs: tiny regulators with great potential". Cell. 107 (7): 823–826. doi: 10.1016/S0092-8674(01)00616-X . PMID   11779458.
  4. 1 2 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ Ambros V (2001). "microRNAs: tiny regulators with great potential". Cell. 107 (7): 823–6. doi: 10.1016/S0092-8674(01)00616-X . PMID   11779458.
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