PubMed Health⌕ Search

Biomedical subjects

A Grishok

Publications and source records attributed to A Grishok.

6 recordsLinked to original sources

Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.

RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA and involves the generation of 21 to 26 nt RNA segments that guide mRNA destruction. In Caenorhabditis elegans, lin-4 and let-7 encode small temporal RNAs (stRNAs) of 22 nt that regulate stage-specific development. Here we show that inactivation of genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations. Further we show that dcr-1, alg-1, and alg-2 are necessary for the maturation and activity of the lin-4 and let-7 stRNAs. Our findings suggest that a common processing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation.

Animals↗

Genetic requirements for inheritance of RNAi in C. elegans.

In Caenorhabditis elegans, the introduction of double-stranded RNA triggers sequence-specific genetic interference (RNAi) that is transmitted to offspring. The inheritance properties associated with this phenomenon were examined. Transmission of the interference effect occurred through a dominant extragenic agent. The wild-type activities of the RNAi pathway genes rde-1 and rde-4 were required for the formation of this interfering agent but were not needed for interference thereafter. In contrast, the rde-2 and mut-7 genes were required downstream for interference. These findings provide evidence for germ line transmission of an extragenic sequence-specific silencing factor and implicate rde-1 and rde-4 in the formation of the inherited agent.

Animals↗

The rde-1 gene, RNA interference, and transposon silencing in C. elegans.

Double-stranded (ds) RNA can induce sequence-specific inhibition of gene function in several organisms. However, both the mechanism and the physiological role of the interference process remain mysterious. In order to study the interference process, we have selected C. elegans mutants resistant to dsRNA-mediated interference (RNAi). Two loci, rde-1 and rde-4, are defined by mutants strongly resistant to RNAi but with no obvious defects in growth or development. We show that rde-1 is a member of the piwi/sting/argonaute/zwille/eIF2C gene family conserved from plants to vertebrates. Interestingly, several, but not all, RNAi-deficient strains exhibit mobilization of the endogenous transposons. We discuss implications for the mechanism of RNAi and the possibility that one natural function of RNAi is transposon silencing.

Amino Acid Sequence↗

Extracellular nucleic acids as possible messengers in regulatory information transfer from immune system to non-lymphoid tissues.

The goal of this review is to connect the information on the regulation of growth and differentiation of non-lymphoid tissues by the immune system and the release/uptake of nucleic acids by living cells (especially by lymphocytes). Nucleic acids are suggested to be the messengers in regulatory information transfer from the immune system to other cells.

Animals↗

Polymorphism in the number of genes encoding long-wavelength-sensitive cone pigments among males with normal color vision.

Examination by direct DNA sequence analysis of the X-linked visual pigment genes in 27 males with normal color vision reveals that almost half have two or more different genes encoding a long-wavelength-sensitive cone pigment. This is counter to the conventional theory proposed from results of Southern hybridization studies that there is a single long-wave pigment gene per X-chromosome. Further, the sequences and consideration of the structure of the X-linked pigment gene array suggest that the majority of the observers (as many as 2/3) have hybrid (or fusion) genes like those that have been proposed to underlie color anomaly. In some observers the long-wave hybrid genes contain a substantial amount of middle-wave sequence, e.g. five observers have hybrid long-wave genes that contain middle-wave sequences that include exon 4. Three of those five have the hybrid as their only long-wave gene, and thus have no other gene that could potentially encode a long-wave pigment. In these subjects, it is the hybrid gene that produces their normal long-wavelength-sensitive cone pigment. The high frequency of hybrid genes indicates that they are normal variant forms of the long-wave gene. Contrary to what is commonly believed, the introduction and the expression of hybrid genes is not sufficient to cause color vision defects.

Base Sequence↗