High impact information on lin-14

• Furthermore, lin-14 and lin-28 are targets of the lin-4 miRNA, and we show that the mRNA levels for these protein-coding genes significantly decrease in response to lin-4 expression [1].
• Mutations that prevent the normal developmental down-regulation of lin-14, activity delay or block VPC division and prevent vulval differentiation [2].
• These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation [3].
• The heterochronic genes lin-4, lin-14, lin-28, and lin-29 control the timing of specific postembryonic developmental events in C. elegans [4].
• Gain-of-function lin-14 mutations cause the level of lin-14 protein to remain high throughout development, resulting in developmental reiterations of early cell lineages [5].

Biological context of lin-14

• The assay is based on quantitating the precocious alae phenotype caused by a mutation that reduces but does not eliminate the function of the X-linked gene lin-14 [6].
• Assessment of X chromosome dosage compensation in Caenorhabditis elegans by phenotypic analysis of lin-14 [6].
• The heterchronic gene lin-14 controls the temporal sequence of developmental events in the Caenorhabditis elegans postembryonic cell lineage [7].
• Heterochronic genes control the timing of vulval development in the C. elegans hermaphrodite. lin-14 or lin-28 loss-of-function mutations cause the vulval precursor cells (VPCs) to enter S phase and to divide one larval stage earlier than in the wild type [2].
• Switching off lin-14 expression during the L1 stage is not triggered by the passage of time per se but, rather, is normally dependent on feeding or the feeding-dependent initiation of postembryonic cell division [8].

Anatomical context of lin-14

• The time of LIN-29 appearance in the hypodermis is controlled by the heterochronic gene pathway: LIN-29 accumulates in the hypodermis abnormally early, during the third larval stage, in loss-of-function lin-14, lin-28 and lin-42 mutants, and fails to accumulate in hypodermis of lin-4 mutants [9].

Regulatory relationships of lin-14

• We provide evidence that lin-14 inhibits a negative regulation that is independent of the lin-4 RNA and involves the gene daf-12, which encodes a nuclear hormone receptor [10].

Other interactions of lin-14

• A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA-RNA interactions with their 3' untranslated regions [11].
• Additionally, in the case of dpy-21 we correlate the change in phenotypic expression of lin-14 with a corresponding change in the lin-14 mRNA transcript level [6].
• Loss of the lim-6 and ceh-14 transcription factors and the developmental timer lin-14 cause not only a loss of zig gene expression but also lead to defects in the maintenance of ventral nerve cord architecture [12].

Analytical, diagnostic and therapeutic context of lin-14

• To identify candidates for genes directly regulated by lin-14, we employed DNA microarray hybridization to compare the mRNA abundance of C. elegans genes in wild-type animals to that in mutants with reduced or elevated lin-14 activity [13].

References