Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs.

mRNA therapeutics offer a potentially universal strategy for the efficient development and delivery of therapeutic proteins. Current mRNA vaccines include chemically modified nucleotides to reduce cellular immunogenicity. Here, we develop an efficient, high-throughput method to measure human translation initiation on therapeutically modified as well as endogenous RNAs.

Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy.

Translation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we data-mined human and mouse heart ribosome profiling analyses and identified a double-stranded RNA (dsRNA) structure within the GATA4 uORF that cooperates with the start codon to augment uORF translation and inhibits mORF translation.

Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy.

Unlabelled: Translation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we identified a double-stranded RNA (dsRNA) structure residing within the uORF that augments uORF translation and inhibits mORF translation.

Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs.

PIWI-interacting small RNAs (piRNAs) protect the germline genome and are essential for fertility. piRNAs originate from transposable element (TE) RNAs, long non-coding RNAs, or 3´ untranslated regions (3´UTRs) of protein-coding messenger genes, with the last being the least characterized of the three piRNA classes. Here, we demonstrate that the precursors of 3´UTR piRNAs are full-length mRNAs and that post-termination 80S ribosomes guide piRNA production on 3´UTRs in mice and chickens.

Glutamyl-Prolyl-tRNA Synthetase Regulates Proline-Rich Pro-Fibrotic Protein Synthesis During Cardiac Fibrosis.

Rationale: Increased protein synthesis of profibrotic genes is a common feature in cardiac fibrosis and heart failure. Despite this observation, critical factors and molecular mechanisms for translational control of profibrotic genes during cardiac fibrosis remain unclear.

Objective: To investigate the role of a bifunctional ARS (aminoacyl-tRNA synthetase), EPRS (glutamyl-prolyl-tRNA synthetase) in translational control of cardiac fibrosis.

Author Correction: Ribosomes guide pachytene piRNA formation on long intergenic piRNA precursors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ribosomes guide pachytene piRNA formation on long intergenic piRNA precursors.

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs essential for fertility. In adult mouse testes, most piRNAs are derived from long single-stranded RNAs lacking annotated open reading frames (ORFs). The mechanisms underlying how piRNA sequences are defined during the cleavages of piRNA precursors remain elusive.

Tumor necrosis factor-like weak inducer of apoptosis regulates quadriceps muscle atrophy and fiber-type alteration in a rat model of chronic obstructive pulmonary disease.

Background: In chronic obstructive pulmonary disease (COPD), weakness and muscle mass loss of the quadriceps muscle has been demonstrated to predict survival and mortality rates of patients. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), as a member of the TNF superfamily, has recently been identified as a key regulator of skeletal muscle wasting and metabolic dysfunction. So our aim was to study the role of TWEAK during quadriceps muscle atrophy and fiber-type transformation in COPD model rats and its possible pathway.

Domestic chickens activate a piRNA defense against avian leukosis virus.

PIWI-interacting RNAs (piRNAs) protect the germ line by targeting transposable elements (TEs) through the base-pair complementarity. We do not know how piRNAs co-evolve with TEs in chickens. Here we reported that all active TEs in the chicken germ line are targeted by piRNAs, and as TEs lose their activity, the corresponding piRNAs erode away.

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells.

Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs).