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The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
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The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
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Journal Article
The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
2000
Overview
The
C. elegans
heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events
1
. Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated
2
. Here we show that
let-7
is a heterochronic switch gene. Loss of
let-7
gene activity causes reiteration of larval cell fates during the adult stage, whereas increased
let-7
gene dosage causes precocious expression of adult fates during larval stages.
let-7
encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3′ untranslated regions of the heterochronic genes
lin-14
,
lin-28
,
lin-41
,
lin-42
and
daf-12
, indicating that expression of these genes may be directly controlled by
let-7
. A reporter gene bearing the
lin-41
3′ untranslated region is temporally regulated in a
let-7
-dependent manner. A second regulatory RNA,
lin-4
, negatively regulates
lin-14
and
lin-28
through RNA–RNA interactions with their 3′ untranslated regions
3
,
4
. We propose that the sequential stage-specific expression of the
lin-4
and
let-7
regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
Analytical, structural and metabolic biochemistry
/ Animals
/ Animals, Genetically Modified
/ Biological and medical sciences
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - growth & development
/ Caenorhabditis elegans Proteins
/ DNA-Binding Proteins - genetics
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Developmental
/ Genes
/ Humanities and Social Sciences
/ letter
/ Mutation
/ Science
/ Transcription Factors - genetics
/ Worms
