miR-146

miR-146
Conserved secondary structure of miR-146 microRNA precursor
Identifiers
Symbol miR-146
Alt. Symbols MIR146
Rfam RF00691
miRBase MI0000477
miRBase family MIPF0000103
Entrez 406938
HUGO 31533
OMIM 610566
RefSeq NR_029897
Other data
RNA type miRNA
Domain(s) Mammalia
GO 0035195
SO 0001244
Locus Chr. 5 q34

miR-146 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.[1] This sequence then associates with RISC which effects RNA interference.[2]

miR-146 is primarily involved in the regulation of inflammation and other process that function in the innate immune system.[3] Loss of functional miR-146 (and mir-145) could predispose an individual to suffer from chromosome 5q deletion syndrome.[4] miR-146 has also been reported to be highly upregulated in osteoarthritis cartilage, and could be involved in its pathogenesis.[5]

Function

miR-146 is thought to be a mediator of inflammation along with another microRNA, mir-155. The expression of miR-146 is upregulated by inflammatory factors such as interleukin 1 and tumor necrosis factor-alpha.[6] miR-146 dysregulates a number of targets which are mostly involved in toll-like receptor pathways that bring about a cytokine response as part of the innate immune system.[3][6] miR-146 operates in a feedback system or "negative regulatory loop"[7] to finely tune inflammatory responses.[4]

Applications

miR-146 could be used as a biomarker for sepsis.[8] In addition it was found to be absent from the exosomes of prion infected cells suggesting it could be used as a biomarker for prion infection.[9] miR-146a could be targeted therapeutically as its depletion has implication in the hyperactive response to infection.[10]

References

  1. ↑ Ambros, V (2001-12-28). "microRNAs: tiny regulators with great potential.". Cell 107 (7): 823–6. doi:10.1016/S0092-8674(01)00616-X. PMID 11779458.
  2. ↑ Gregory, RI; Chendrimada, TP, Cooch, N, Shiekhattar, R (2005-11-18). "Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.". Cell 123 (4): 631–40. doi:10.1016/j.cell.2005.10.022. PMID 16271387.
  3. ↑ 3.0 3.1 Sonkoly, E; Ståhle, M; Pivarcsi, A (Apr 2008). "MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation.". Seminars in cancer biology 18 (2): 131–40. doi:10.1016/j.semcancer.2008.01.005. PMID 18291670.
  4. ↑ 4.0 4.1 Quinn, SR; O'Neill, LA (Jul 2011). "A trio of microRNAs that control Toll-like receptor signalling.". International immunology 23 (7): 421–5. doi:10.1093/intimm/dxr034. PMID 21652514.
  5. ↑ Yamasaki, K; Nakasa, T; Miyaki, S; Ishikawa, M; Deie, M; Adachi, N; Yasunaga, Y; Asahara, H; Ochi, M (Apr 2009). "Expression of MicroRNA-146a in osteoarthritis cartilage.". Arthritis and rheumatism 60 (4): 1035–41. doi:10.1002/art.24404. PMC 2670476. PMID 19333945.
  6. ↑ 6.0 6.1 Sheedy, FJ; O'Neill, LA (Dec 2008). "Adding fuel to fire: microRNAs as a new class of mediators of inflammation.". Annals of the rheumatic diseases. 67 Suppl 3: iii50–5. doi:10.1136/ard.2008.100289. PMID 19022814.
  7. ↑ Ma, X; Becker Buscaglia, LE, Barker, JR, Li, Y (Jun 2011). "MicroRNAs in NF-kappaB signaling.". Journal of molecular cell biology 3 (3): 159–66. doi:10.1093/jmcb/mjr007. PMC 3104013. PMID 21502305.
  8. ↑ Gîză, DE; Vasilescu, C (Sep–Oct 2010). "[MicroRNA's role in sepsis and endotoxin tolerance. More players on the stage].". Chirurgia (Bucharest, Romania : 1990) 105 (5): 625–30. PMID 21141085.
  9. ↑ Bellingham, SA; Coleman, BF, Hill AF (Sep 2012). "Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells.". Nucleic Acids Research 40 (21): 10937–49. doi:10.1093/nar/gks832. PMC 3505968. PMID 22965126.
  10. ↑ O’Connell, R; Rao, D; Baltimore, D (2012). "microRNA Regulation of Inflammatory Responses". Annual Review of Immunology 30: 295–312. doi:10.1146/annurev-immunol-020711-075013. PMID 22224773.

Further reading

See also

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