Palmer ML et al. (2006) Cell Biochem Biophys "RNA interference and ion channel physiology."

Palmer ML, Fahrenkrug SC, O'grady SM

[Cell Biochem Biophys, 2006]

RNA interference (RNAi), through expression of small, double-stranded RNAs or short hairpin RNAs, produces sequence-specific mRNA degradation and decreased gene expression. Since its discovery in 1998 (Fire et al., 1998, Nature 391, 806-811), RNAi has rapidly become one of the most widely used technologies for exploring gene function in eukaryotic cells. Although the topic of RNAi has been the subject of a large number of excellent reviews, the focus of this article is on its application to the study of ion channel physiology in animal cells. In this regard, RNAi has provided definitive identification of ion channel subtypes responsible for both basal and stimulated ion conduction across the plasma membrane of several cell types. The approach has been particularly effective in identifying and establishing the contribution of auxiliary subunits and regulatory proteins to the overall function of ion channel complexes. Moreover, selective knockdown of ion channel expression has been a valuable means of demonstrating roles in the development of specific cell domains and in the normal growth of certain cell types. In this review, a brief description of the general mechanism of RNAi is presented, followed by a discussion of some important considerations for the in vitro application of this technology and in producing transgenic animals as models for human disease. We then describe several examples of where RNAi has been used to investigate the physiological role of ion channels in cells from model organisms (Caenorhabditis elegans and Drosophila melanogaster) and in mammalian cells.

Chen EB et al. (1998) Trends Genet "Understanding cell migration guidance: lessons from sex myoblast migration in C. elegans."

Chen EB, Stern MJ

[Trends Genet, 1998]

Studies of sex myoblast (SM) migration in the nematode Caenorhabditis elegans have shown that multiple guidance mechanisms cooperate to ensure the accurate and reproducible targeting of the SMs. Many issues arise in the analysis of SM migration, including the action of multiple guidance mechanisms, redundant sources of guidance information, the multiple uses of molecular components, and whether factors affect cell fate determination events or the guidance mechanisms themselves. These issues are common to many cell migration events and make the analysis of SM migration instructive to our general understanding of how cell migrations are controlled.

Hutagalung AH et al. (2002) J Cell Sci "The UCS family of myosin chaperones."

Landsverk ML, Hutagalung AH, Price MG, Epstein HF

[J Cell Sci, 2002]

The canonical UCS (UNC-45/Crol/She4p) protein, Caenorhabditis elegans UNC-45, was one of the earliest molecules to be shown genetically to be necessary for sarcomere assembly. Genetic analyses of homologues in several fungal species indicate that the conserved UCS domain functionally interacts with conventional type II and unconventional type V myosins. In C. elegans and other invertebrate species, UNC-45 and its orthologues interact with both sarcomeric and non-sarcomeric myosins whereas, in vertebrates, there are two UNC-45 isoforms: a general cell (GC) and a striated muscle (SM) isoform. Although the mechanism of action of UCS proteins is unknown, recent biochemical studies suggest that they may act as molecular chaperones that facilitate the folding and/or maturation of myosin.

Jones TA et al. (2009) RNA Biol "A survey of nematode SmY RNAs."

Marz M, Eddy SR, Stadler PF, Jones TA, Otto W

[RNA Biol, 2009]

SmY RNAs are a family of approximately 70-90 nt small nuclear RNAs found in nematodes. In C. elegans, SmY RNAs copurify in a small ribonucleoprotein (snRNP) complex related to the SL1 and SL2 snRNPs that are involved in nematode mRNA trans-splicing. Here we describe a comprehensive computational analysis of SmY RNA homologs found in the currently available genome sequences. We identify homologs in all sequenced nematode genomes in class Chromadorea. We are unable to identify homologs in a more distantly related nematode species, Trichinella spiralis (class: Dorylaimia), and in representatives of non-nematode phyla that use trans-splicing. Using comparative RNA sequence analysis, we infer a conserved consensus SmY RNA secondary structure consisting of two stems flanking a consensus Sm protein binding site. A representative seed alignment of the SmY RNA family, annotated with the inferred consensus secondary structure, has been deposited with the Rfam RNA families database.