Presentation/Session Information

Session Information

Session Title: Evolution, Ecology, and Germline Development Session Type: Parallel
Session Location: De Neve Auditorium Session Time: Fri, Jun 26 8:30AM - 11:30AM

Presentation Information

Program Number: 105 Presentation Time: 10:06AM - 10:18AM

Presentation Content

A long non-coding RNA acts in developmental timing by repressing LIN-28.Karin Kiontke 1, R. Antonio Herrera 1, Edward Vuong 2, Douglas S. Portman 2, David H. A. Fitch 1. 1)Department of Biology, New York University, New York, NY; 2)Center for Neural Development and Disease, University of Rochester, Rochester, NY

Developmental timing in C. elegans is regulated by the heterochronic pathway, a conserved developmental program that features temporal waves of miRNA expression. This mechanism coordinates multiple stage-specific developmental events, including the late-larval morphogenesis that generates the rounded adult male tail tip. We identified a novel gene, lep-5 (H36L18.2), that regulates the timing of tail tip morphogenesis in L4 males. Loss of lep-5 results in absent or delayed morphogenesis, such that adult males retain a juvenile pointed tail tip, while overexpression of lep-5 causes premature retraction. Some mutant adults undergo an additional molt, thus demonstating that the activity of lep-5 is not restricted to the tail tip. However, lep-5 mutants do not exhibit any defects in the development of the lateral seam. Unexpectedly, lep-5 functions not as a protein or miRNA, but rather as a novel long noncoding RNA (lncRNA). SL1-spliced lep-5 lncRNA is predicted to adopt a complex secondary structure with multiple stem-loops, at least two of which are necessary for its function. lep-5 is highly conserved within Caenorhabditis but could not be identified outside of this genus. The expression of lep-5 is temporally regulated with a peak between late L2 and mid L3. During this time, lep-5 lncRNA is visible via RNA smFISH in many tissues except the gut and germline, with a notable concentration in the nervous system.

By testing genetic interactions and performing Western blot and qPCR analysis, we determined that lep-5 lncRNA down-regulates LIN-28 protein levels post-transcriptionally without affecting LIN-28 mRNA levels. We further found that Lep-5 acts on the 3’UTR of the LIN-28 mRNA independent of previously identifid miRNA binding sites. Although the mechanism for its activity is not yet known, lep-5 represents the first example of a functional lncRNA in C. elegans. Furthermore, adding a lncRNA to the multiple miRNAs that act in the heterochronic pathway highlights the striking importance of RNA-mediated regulation in developmental timing.

Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

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