Specific and potent RNAi in the nucleus of human cells

Robb, G. Brett; Brown, Kirk M.; Khurana, Jaspreet S.; Rana, Tariq M.

doi:10.1038/nsmb886

Cited by 290 publications

(269 citation statements)

References 47 publications

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“…Interestingly, they demonstrated that, at least for miR29b, it is a distinctive hexanucleotide element (AGUGUU) that distinguishes miR-29b from its family member miR-29a and guides its nucleus import. Consistently, studies have also reported the presence of active miRNA effectors, such as Argonaute proteins, in the nucleus (6). These findings suggest that there are mechanisms to guide the cytoplasmic-nuclear transport of miRNAs and Argonaute proteins and that miRNAs, after re-entering into the nucleus, may also have biological functions.…”

supporting

confidence: 64%

Importin 8 Regulates the Transport of Mature MicroRNAs into the Cell Nucleus

Yao¹,

Liu²,

Wang

et al. 2014

Journal of Biological Chemistry

124

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supporting

confidence: 64%

Importin 8 Regulates the Transport of Mature MicroRNAs into the Cell Nucleus

Yao¹,

Liu²,

Wang

et al. 2014

Journal of Biological Chemistry

124

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“…Indeed, previous reports stated that nuclear-localized ncRNA such as RN7SK (Robb et al 2005;Berezhna et al 2006), MALAT1 (Tano et al 2010;Miyagawa et al 2012), and NEAT1 (Clemson et al 2009) could be silenced by siRNAs. There are at least two possibilities for silencing nuclear-localized RNA by siRNA: (1) The component of siRNA-induced silencing localized in the nucleus can function to cleave endogenous nuclear target RNAs in the nucleus (Robb et al 2005). (2) The cytoplasmic RISC cleaves endogenous nuclear target RNAs at the M phase of the cell cycle when the nuclear envelope disassembles and nuclear components, including nuclear ncRNAs, are contacted by cytoplasmic components such as the RISC complex.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals

Tani¹,

Mizutani²,

Salam³

et al. 2012

Genome Res.

398

422

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Mammalian genomes produce huge numbers of noncoding RNAs (ncRNAs). However, the functions of most ncRNAs are unclear, and novel techniques that can distinguish functional ncRNAs are needed. Studies of mRNAs have revealed that the half-life of each mRNA is closely related to its physiological function, raising the possibility that the RNA stability of an ncRNA reflects its function. In this study, we first determined the half-lives of 11,052 mRNAs and 1418 ncRNAs in HeLa Tet-off (TO) cells by developing a novel genome-wide method, which we named 59-bromo-uridine immunoprecipitation chase-deep sequencing analysis (BRIC-seq). This method involved pulse-labeling endogenous RNAs with 59-bromo-uridine and measuring the ongoing decrease in RNA levels over time using multifaceted deep sequencing. By analyzing the relationship between RNA half-lives and functional categories, we found that RNAs with a long half-life (t 1/2 $ 4 h) contained a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short halflife (t 1/2 < 4 h) included known regulatory ncRNAs and regulatory mRNAs. The stabilities of a significant set of short-lived ncRNAs are regulated by external stimuli, such as retinoic acid treatment. In particular, we identified and characterized several novel long ncRNAs involved in cell proliferation from the group of short-lived ncRNAs. We designated this novel class of ncRNAs with a short half-life as Short-Lived noncoding Transcripts (SLiTs). We propose that the strategy of monitoring RNA half-life will provide a powerful tool for investigating hitherto functionally uncharacterized regulatory RNAs.

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“…Mammalian studies are consistent with this scenario; sRNA-loaded RISC in the cytoplasm consists of a large AGO-based complex, whereas in the nucleus, RISC consists of little more than AGO and its loaded sRNA. [75][76][77] Figure 4B illustrates a proposed pathway for miRNA-directed expressional regulation of nuclear-localized transcripts. Recent studies have localized the miRNA biogenesis machinery proteins DCL1, DRB1 and SE to the nucleus specialized D-bodies.…”

Section: Discussionmentioning

confidence: 99%