Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease.

The polyglutamine expansion of huntingtin (mHTT) causes Huntington disease (HD) and neurodegeneration, but the mechanisms remain unclear. Here, we found that mHtt promotes ribosome stalling and suppresses protein synthesis in mouse HD striatal neuronal cells. Depletion of mHtt enhances protein synthesis and increases the speed of ribosomal translocation, while mHtt directly inhibits protein synthesis in vitro.

A Mitochondrial Micropeptide Is Required for Activation of the Nlrp3 Inflammasome.

Functional peptides encoded by short open reading frames are emerging as important mediators of fundamental biological processes. In this study, we identified a micropeptide produced from a putative long noncoding RNA (lncRNAs) that is important in controlling innate immunity. By studying lncRNAs in mice macrophages, we identified lncRNA 1810058I24Rik, which was downregulated in both human and murine myeloid cells exposed to LPS as well as other TLR ligands and inflammatory cytokines.

Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins.

Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells and living organisms. However, their delivery into target cells can be technically challenging when working with primary cells or in vivo. Here, we use engineered murine leukemia virus-like particles loaded with Cas9-sgRNA ribonucleoproteins (Nanoblades) to induce efficient genome-editing in cell lines and primary cells including human induced pluripotent stem cells, human hematopoietic stem cells and mouse bone-marrow cells.

PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process.

[An intimate look at the viral replication cycle through ribosome profiling].

Next Generation Sequencing (NGS) techniques have revolutionized most biomedical research fields over the past decade by allowing a broader vision on biological processes that occur at the molecular level. Among these, ribosome profiling or footprinting is a powerful tool to study mRNA translation in a transcriptome-wide manner. Ribosome profiling has been used to study the impact of translational control of gene expression under many different cellular conditions including viral infections.

A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation.

Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs).

Perspective: The RNA exosome, cytokine gene regulation and links to autoimmunity.

The RNA exosome is a highly conserved exoribonuclease complex that is involved in RNA processing, quality control and turnover regulation. The exosome plays pleiotropic functions by recruiting different cofactors that regulate its target specificity. Recently, the exosome has been implicated in the regulation of immune processes including cytokine production and negative regulation of innate sensing of nucleic acids.