Cytoplasmic foci are sites of mRNA decay in human cells

By Nicolas Cougot, S. Babajko, Bertrand Séraphin. Journal of Cell Biology, 2004

684 citations recorded by the source corpus.

Understanding gene expression control requires defining the molecular and cellular basis of mRNA turnover. We have previously shown that the human decapping factors hDcp2 and hDcp1a are concentrated in specific cytoplasmic structures. Here, we show that hCcr4, hDcp1b, hLsm, and rck/p54 proteins related to 5′–3′ mRNA decay also localize to these structures, whereas DcpS, which is involved in cap nucleotide catabolism, is nuclear. Functional analysis using fluorescence resonance energy transfer revealed that hDcp1a and hDcp2 interact in vivo in these structures that were shown to differ from the previously described stress granules. Our data indicate that these new structures are dynamic, as they disappear when mRNA breakdown is abolished by treatment with inhibitors. Accumulation of poly(A)+ RNA in these structures, after RNAi-mediated inactivation of the Xrn1 exonuclease, demonstrates that they represent active mRNA decay sites. The occurrence of 5′–3′ mRNA decay in specific subcellular locations in human cells suggests that the cytoplasm of eukaryotic cells may be more organized than previously anticipated.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6c71e1d15e65a6657793145064e113e4470da5a6

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Citations in the corpus

How do microRNAs regulate gene expression? (2008, background): “P-bodies not only contain (untranslated) mRNA and especially mRNA decay intermediates, but they require this RNA for their integrity (57, 60 ).”
P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. (2012, background): “This possibility is supported by the observation that P-bodies increase in number and size when mRNA decay is inhibited at the stage of decapping by deletion of Dcp1 or after decapping by the deletion of Xrn1 (Sheth and Parker 2003; Cougot et al. 2004).”
Mammalian stress granules and processing bodies. (2007, background): “Conversely, knockdown experiments indicate that reduced levels of many individual PB components (e.g., DCP1, Lsm1, GW182, hedls/GE-1 ( Cougot et al., 2004; Stoecklin et al., 2005; Yu et al., 2005)) will decrease the numbers and size of PBs.”
Stress granules and processing bodies are dynamically linked sites of mRNP remodeling (2005, background): “AntiDcp2was a gift of B. Seraphin (Centre de Genetique Moleculaire, Gif-surYvette, France) and M. Kildejian (Rutgers University, Piscataway, NJ).”
Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies (2005, background): “Subsequently, other enzymes involved in mRNA degradation, such as the decapping enzymes Dcp1a and Dcp2, were detected in these microscopically discrete foc”
General translational repression by activators of mRNA decapping. (2005, background): “Fourth, RCK/p54 accumulates within P bodies in mammalian cells (Cougot et al., 2004), and RCK/p54 knockdowns with siRNA reduce P body formation (Andrei et al.”
Processing bodies require RNA for assembly and contain nontranslating mRNAs. (2005, background): “P-bodies include the decapping enzyme (Dcp1p/Dcp2p), activators of decapping, Dhh1p (referred to as RCK in mammals), Pat1p, Lsm1–7p, Edc3p, and the 5 –3 exonuclease Xrn1p (Bashkirov et al. 1997; Ingelfinger et al. 2002; Lykke-Andersen 2002; van Dijk et al. 2002; Sheth and Parker 2003; Cougot et al. ”
Control of translation and mRNA degradation by miRNAs and siRNAs. (2006, background): “In a range of eukaryotic cells, including yeast and mammals, the decapping enzyme (consisting of Dcp1/Dcp2), Xrn1p, and several activators of decapping are concentrated in specific cytoplasmic foci known as cytoplasmic processing bodies (P-bodies, also referred to as GW-bodies), which can be sites o”
High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. (2018, background): “The decapping enzymes DCP1 and DCP2, as well as the components of the major deadenylase CCR4-NOT, are only detected in PBs (Cougot et al., 2004), whereas the SG assembly factor G3BP1, the poly(A)-binding protein PABPC1, and the translation initiation factors eIF4G and eIF3 are restricted to SGs (Ked”
P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing (2007, background): “, DCP1, DCP2, CCR4, and CAF1) localize to P bodies (4, 16, 17, 44, 49).”
P bodies and the control of mRNA translation and degradation. (2007, background): “Conversely, when the catalytic steps of decapping or 5 0 to 3 0 exonuclease digestion are inhibited in yeast or mammalian cells, P bodies increase in size (Sheth and Parker, 2003; Cougot et al., 2004; Andrei et al., 2005). mRNAs can also exit the P body state and reenter translation .”
MicroRNA: Biogenesis, Function and Role in Cancer (2010, background): “P-bodies contain mRNA along with a variety of enzymes and factors required for processes such as mRNA decapping, deadenylation, RNA degradation and translational repression [164, 182].”