^a Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, 02114

^b Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire, 03755

Abstract

Thelin-4gene encodes a small RNA that is required to translationally represslin-14toward the end of the first larval stage ofCaenorhabditis elegansdevelopment. To determine if the timing of LIN-14 protein down-regulation depends on the temporal profile oflin-4RNA level, we analyzed the stage-specificity oflin-4RNA expression during wild-type development and examined the phenotypes of transgenic worms that overexpresslin-4RNA during the first larval stage. We found thatlin-4RNA first becomes detectable at approximately 12 h of wild-type larval development and rapidly accumulates to nearly maximum levels by 16 h. This profile oflin-4RNA accumulation corresponded to the timing of LIN-14 protein down-regulation. Transgenic strains that express elevated levels oflin-4RNA prior to 12 h of development display reduced levels of LIN-14 protein and precocious phenotypes consistent with abnormally early loss oflin-14activity. These results indicate that the temporal profile oflin-4RNA accumulation specifies the timing of LIN-14 down-regulation and thereby controls the timing of postembryonic developmental events.

Author Keywords: heterochronic genes;lin-4RNA; LIN-14, developmental timing;C. elegans.

¹ To whom correspondence should be addressed. Fax: (603) 646-1347. E-mail:vambros@dartmouth.edu.