RESUMO
Understanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2-8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved factor in telomere maintenance.
Assuntos
Proteínas Nucleares/genética , Fosfoproteínas/genética , Proteínas de Protozoários/genética , RNA Fúngico/genética , DNA Polimerase Dirigida por RNA/genética , RNA/genética , Ribonucleoproteínas/genética , Schizosaccharomyces/genética , Telomerase/genética , Motivos de Aminoácidos , Sequência Conservada , Expressão Gênica , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Ligação Proteica , Proteínas de Protozoários/metabolismo , RNA/metabolismo , Estabilidade de RNA , RNA Fúngico/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Ribonucleoproteínas/metabolismo , Schizosaccharomyces/metabolismo , Telomerase/metabolismo , Telômero/química , Telômero/ultraestrutura , Tetrahymena thermophila/genética , Tetrahymena thermophila/metabolismoRESUMO
We agree with the author that a quantitative analysis of the predictive nature of the metrics used in graduate student admissions is a worthy pursuit and value the sincere intentions behind the UCSF Tetrad study. However, these types of analyses would benefit from the same rigorous approaches that we employ in our other research endeavors. As UCSF Tetrad graduates with diverse careers in academia, medicine, industry, and publishing, we hope that the definition of success in graduate school can be as thoughtfully and scientifically examined as the measurements used to select the next young people to follow in our footsteps.
Assuntos
Educação de Pós-Graduação , Critérios de Admissão Escolar/tendências , Estudantes/estatística & dados numéricos , Feminino , Humanos , MasculinoRESUMO
The zebrafish, Danio rerio, is emerging as an important model organism for the pathophysiological study of some human kidney diseases, but the sites of expression and physiological roles of a number of protein orthologues in the zebrafish nephron remain mostly undefined. Here we show that a zebrafish potassium channel is orthologous to the mammalian kidney potassium channel, ROMK. The cDNA (kcnj1) encodes a protein (Kcnj1) that when expressed in Xenopus laevis oocytes displayed pH- and Ba2+-sensitive K+-selective currents, but unlike the mammalian channel, was completely insensitive to the peptide inhibitor tertiapin-Q. In the pronephros, kcnj1 transcript expression was restricted to a distal region and overlapped with that of sodiumchloride cotransporter Nkcc, chloride channel ClC-Ka, and ClC-Ka/b accessory subunit Barttin, indicating the location of the diluting segment. In a subpopulation of surface cells, kcnj1 was coexpressed with the a1a.4 isoform of the Na+/K+-ATPase, identifying these cells as potential K+ secretory cells in this epithelium. At later stages of development, kcnj1 appeared in cells of the developing gill that also expressed the a1a.4 subunit.Morpholino antisense-mediated knockdown of kcnj1 was accompanied by transient tachycardia followed by bradycardia, effects consistent with alterations in extracellular K+ concentration in the embryo.Our findings indicate that Kcnj1 is expressed in cells associated with osmoregulation and acts as a K+ efflux pathway that is important in maintaining extracellular levels of K+ in the developing embryo.
