View source for Lsy-6 microRNA

{{Infobox rfam
| Name = lsy-6
| image =
| width =
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| Symbol = lsy-6
| AltSymbols =
| Rfam = RF00823
| miRBase_family = MIPF0000265
| RNA_type = [[microRNA]]
| Tax_domain = ''[[Eukaryote|Eukaryota]]; [[Animal|Metazoa]]; [[Nematode|Nematoda]];''
| HGNCid =
| OMIM =
}}
'''lsy-6 microRNA''' belongs to the class of [[microRNA|miRNAs]]; these function to regulate the expression levels of other genes by several mechanisms. lsy-6 is a short [[non-coding RNA]] molecule and the first miRNA identified as having a role in nervous system development. It regulates left-right neuronal asymmetry in the nematode worm ''[[Caenorhabditis elegans]]''.
==Left-right asymmetry through the ''cog-1'' gene==
ASEL and ASER are a pair of [[bilateral symmetry|bilateral]] taste receptor [[neuron]]s thought to be responsible for the asymmetrical pattern of chemoreceptor gene expression in ''C. elegans''. These two gustatory neurons are bilaterally symmetric morphologically, as well as with regards to their connectivity, position and gene expression patterns. However, they are left-right asymmetric in their expression of specific signalling molecules.<ref name="pmid14685240">{{cite journal | vauthors = Johnston RJ, Hobert O | title = A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans | journal = Nature | volume = 426 | issue = 6968 | pages = 845–849 | date = December 2003 | pmid = 14685240 | doi = 10.1038/nature02255 }}</ref> The ASE neuron is extremely sensitive to the correct dosage of ''cog-1'', an Nkx-type [[homeobox]] gene, and extra copies of this gene will readily produce left/right asymmetry defects.
lsy-6 is responsible for control of [[COG1|cog-1]] expression, as transcriptional mechanisms alone are not sufficient for this regulation. lsy-6 and cog-1 are initially co-expressed by both ASEL and ASER after birth, but their expression later becomes restricted to one of the two ASE neurons (ASEL for lsy-6 and ASER for cog-1).  lsy-6 codes for a 21-nt miRNA, which in turn binds to a single complementary site in the 3′ UTR of the ''cog-1'' gene. This interaction is only seen in the ASEL cell type (not the ASER), thus causing an asymmetric cog-1 distribution. It has been observed that a removal of lsy-6 leads to an altered transcription of cog-1 in ASEL, indicating that despite expressing lsy-6, the ASEL neuron does not transcribe cog-1.<ref name="pmid14685240" />
==Further expression==
lsy-6 is additionally expressed in several other neuron types, including labial [[sensory neuron]]s and PVQ ventral cord [[interneuron]]s.<ref name="pmid14685240" />
==lsy-6/lsy-2 Feedback Loop==
The expression of lsy-6 is itself regulated by lsy-2, a zinc finger [[transcription factor]].<ref name="pmid16291785">{{cite journal | vauthors = Johnston RJ, Hobert O | title = A novel C. elegans zinc finger transcription factor, lsy-2, required for the cell type-specific expression of the lsy-6 microRNA | journal = Development | volume = 132 | issue = 24 | pages = 5451–5460 | date = December 2005 | pmid = 16291785 | doi = 10.1242/dev.02163 | doi-access = free }}</ref> Interaction of lsy-2 with lsy-6 has been found to be cell-type specific and there is complete loss of lsy-6 expression in lsy-2 mutant animals. A bistable feedback loop required for ASE laterality is in place, consisting of miRNAs lsy-6, mir-273, and their respective transcription factors cog-1 and die-1. Whilst lsy-6 is expressed in ASEL but not ASER and regulates the expression of the downstream transcription factor cog-1,<ref name="pmid18463285">{{cite journal | vauthors = Didiano D, Hobert O | title = Molecular architecture of a miRNA-regulated 3′ UTR | journal = RNA | volume = 14 | issue = 7 | pages = 1297–1317 | date = July 2008 | pmid = 18463285 | pmc = 2441980 | doi = 10.1261/rna.1082708 }}</ref> mir-273 expression is strongly biased towards ASER and exhibits complementarity to the mRNA of the die-1 transcription factor. die-1 is regulated at a post-transcriptional level and controls chemosensory laterality by activating the expression of lsy-6 in ASEL only.<ref name="pmid15306811">{{cite journal | vauthors = Chang S, Johnston RJ, Frøkjaer-Jensen C, Lockery S, Hobert O | title = MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode | journal = Nature | volume = 430 | issue = 7001 | pages = 785–789 | date = August 2004 | pmid = 15306811 | doi = 10.1038/nature02752 }}</ref> Expression of die-1 in ASER is downregulated through two sites in its [[three prime untranslated region|3′ UTR]] region.
== See also ==
* [[MicroRNA]]
== References ==
{{reflist|2}}
== External links ==
* {{miRBase|id=MIPF0000265|name=lsy-6}}
* {{Rfam|id=RF00823|name=lsy-6 microRNA family}}
{{miRNA precursor families}}
[[Category:MicroRNA]]
[[Category:Non-coding RNA]]