RESUMO
When mRNAs have been transcribed and processed in the nucleus, they are exported to the cytoplasm for translation. This export is mediated by the export receptor heterodimer Mex67-Mtr2 in the yeast Saccharomyces cerevisiae (TAP-p15 in humans)1,2. Interestingly, many long non-coding RNAs (lncRNAs) also leave the nucleus but it is currently unclear why they move to the cytoplasm3. Here we show that antisense RNAs (asRNAs) accelerate mRNA export by annealing with their sense counterparts through the helicase Dbp2. These double-stranded RNAs (dsRNAs) dominate export compared with single-stranded RNAs (ssRNAs) because they have a higher capacity and affinity for the export receptor Mex67. In this way, asRNAs boost gene expression, which is beneficial for cells. This is particularly important when the expression program changes. Consequently, the degradation of dsRNA, or the prevention of its formation, is toxic for cells. This mechanism illuminates the general cellular occurrence of asRNAs and explains their nuclear export.
Assuntos
Transporte Ativo do Núcleo Celular , Núcleo Celular , Regulação Fúngica da Expressão Gênica , Transporte de RNA , RNA Antissenso , RNA de Cadeia Dupla , RNA Mensageiro , Saccharomyces cerevisiae , Núcleo Celular/metabolismo , Citoplasma/metabolismo , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , RNA Antissenso/metabolismo , RNA Antissenso/genética , RNA de Cadeia Dupla/metabolismo , RNA de Cadeia Dupla/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est and the Pop proteins. This partly matured telomerase is re-imported into the nucleus via Mtr10 and a novel TLC1-import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation in CSE1 leads to the amplification of Y' elements in the terminal chromosome regions and thus elongated telomere ends. Cse1 does not only support TLC1 import, but also the Sm-ring stabilization on the RNA enableling Mtr10 contact and nuclear import. Thus, Sm-ring formation and import factor contact resembles a quality control step in the maturation process of the telomerase. The re-imported immature TLC1 is finally trimmed into the 1158 nucleotides long mature form via the nuclear exosome. TMG-capping of TLC1 finalizes maturation, leading to mature telomerase.
Assuntos
Proteínas de Transporte Nucleocitoplasmático/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Telomerase/metabolismo , Transporte Ativo do Núcleo Celular , Citoplasma/metabolismo , Regulação Fúngica da Expressão Gênica , Modelos Biológicos , Mutação , Proteínas de Transporte Nucleocitoplasmático/genética , Ligação Proteica , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Telomerase/genéticaRESUMO
Kinneretia sp. strain DAIF2 was isolated from a eutrophic freshwater pond. The genome consists of a single chromosome (6,010,585 bp) with a GC content of 69.3%. The whole-genome-based phylogeny of DAIF2 revealed a closest relation to the genus Kinneretia.