Faculty Opinions recommendation of Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies.

Tristetraprolin (TTP) destabilizes AU-rich element (ARE)-containing mRNA by directly binding with their 3′UTR. P38 stimulation substantially increases ARE-mRNA stability, at least through repressing TTP. However, the mechanism by which P38 keeps TTP inactive has not been fully understood. TTP and ARE-mRNA localize to processing bodies (PBs), the mRNA granules associated with mRNA silencing. Here, we detected the influence of P38 on TTP localization within PBs and found that P38 regulates TTP localization within PBs. Through luciferase-based systems, we demonstrated that PBs depletion significantly increased ARE-mRNA stability inhibited by TTP. Additionally, we provided evidence that the microRNA-induced silencing complex (miRISC) core member Ago2 is required for TTP distribution within PBs. Importantly, the cooperation of TTP and Ago2 is a prerequisite for effective ARE-mRNA degradation. Moreover, Dcp1a and Dcp2 act downstream of Ago2 and TTP engaging in ARE-mRNA decay. Finally, we demonstrated that P38 activation represses the interaction between TTP and Ago2 due to TTP phosphorylation, which impairs TTP localization within PBs and ARE-mRNA degradation. Collectively, our study revealed a novel mechanism through which P38 activation repressed the cooperation of TTP with Ago2, thus ensuring that ARE-mRNA does not associate with PBs and remains stable.

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The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100073544 ◽

1973 ◽

Vol 31 ◽

pp. 620-621

Author(s):

J. M. Barrett ◽

P. M. Heidger

Keyword(s):

Fine Structure ◽

Proximal Tubule ◽

Rat Kidney ◽

Renal Proximal Tubule ◽

Convincing Evidence ◽

Cytoplasmic Bodies ◽

Rat Renal Proximal Tubule ◽

Renal Proximal Tubule Cells ◽

Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

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Albumin-Induced Endocytic Vacuoles in Tetrahymena Pyrijormis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100117091 ◽

1975 ◽

Vol 33 ◽

pp. 694-695

Author(s):

L. J. Brenner ◽

D. G. Osborne ◽

B. L. Schumaker

Keyword(s):

Electron Microscopy ◽

Bovine Serum Albumin ◽

Bovine Serum ◽

Protein Concentration ◽

Tetrahymena Pyriformis ◽

Sequence Of Events ◽

Cytoplasmic Bodies ◽

Food Vacuoles ◽

Mouse Ascites ◽

Normal Human

Exposure of the ciliate, Tetrahymena pyriformis, strain WH6, to normal human or rabbit sera or mouse ascites fluids induces the formation of large cytoplasmic bodies. By electron microscopy these (LB) are observed to be membrane-bounded structures, generally spherical and varying in size (Fig. 1), which do not resemble the food vacuoles of cells grown in proteinaceous broth. The possibility exists that the large bodies represent endocytic vacuoles containing material concentrated from the highly nutritive proteins and lipoproteins of the sera or ascites fluids. Tetrahymena mixed with bovine serum albumin or ovalbumin solutions having about the same protein concentration (7g/100 ml) as serum form endocytic vacuoles which bear little resemblance to the serum-induced LB. The albumin-induced structures (Fig. 2) are irregular in shape, rarely spherical, and have contents which vary in density and consistency. In this paper an attempt is made to formulate the sequence of events which might occur in the formation of the albumin-induced vacuoles.

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Influence of nascent polypeptide positive charges on translation dynamics

Biochemical Journal ◽

10.1042/bcj20200303 ◽

2020 ◽

Vol 477 (15) ◽

pp. 2921-2934

Author(s):

Rodrigo D. Requião ◽

Géssica C. Barros ◽

Tatiana Domitrovic ◽

Fernando L. Palhano

Keyword(s):

Mrna Decay ◽

Translation Termination ◽

Published Data ◽

Translation Efficiency ◽

Amino Acid Residues ◽

High Concentration ◽

Strong Argument ◽

Translation Arrest ◽

Exit Tunnel ◽

Positively Charged

Protein segments with a high concentration of positively charged amino acid residues are often used in reporter constructs designed to activate ribosomal mRNA/protein decay pathways, such as those involving nonstop mRNA decay (NSD), no-go mRNA decay (NGD) and the ribosome quality control (RQC) complex. It has been proposed that the electrostatic interaction of the positively charged nascent peptide with the negatively charged ribosomal exit tunnel leads to translation arrest. When stalled long enough, the translation process is terminated with the degradation of the transcript and an incomplete protein. Although early experiments made a strong argument for this mechanism, other features associated with positively charged reporters, such as codon bias and mRNA and protein structure, have emerged as potent inducers of ribosome stalling. We carefully reviewed the published data on the protein and mRNA expression of artificial constructs with diverse compositions as assessed in different organisms. We concluded that, although polybasic sequences generally lead to lower translation efficiency, it appears that an aggravating factor, such as a nonoptimal codon composition, is necessary to cause translation termination events.

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