Ribosome profiling reveals dynamic translational landscape following X-ray irradiation.

X-ray irradiation induces widespread changes in gene expression. Positioned at the bottom of the central dogma, translational regulation responds swiftly to environmental stimuli, fine-tuning protein levels. However, the global view of mRNA translation following X-ray exposure remains unclear.

SIRT6 Inhibits Anoikis of Colorectal Cancer Cells by Down-Regulating NDRG1.

Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the epigenetic regulation of this process remains to be explored. Here, we demonstrate that the histone deacetylase sirtuin 6 (SIRT6) plays a pivotal role in conferring anoikis resistance to colorectal cancer (CRC) cells.

Activation of METTL3 Promotes White Adipose Tissue Beiging and Combats Obesity.

Unlabelled: The induction of beige adipocytes in white adipose tissue (WAT), also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains to be studied. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging in mice.

Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice.

Obesity, one of the most serious public health issues, is caused by the imbalance of energy intake and energy expenditure. N(6)-methyladenosine (mA) RNA modification has been recently identified as a key regulator of obesity, while the detailed mechanism is elusive. Here, we find that YTH RNA binding protein 1 (YTHDF1), an mA reader, acts as an essential regulator of white adipose tissue metabolism.

The RNA m6A Reader YTHDF1 Is Required for Acute Myeloid Leukemia Progression.

Unlabelled: N6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myelogenous leukemia (AML). Identification of the key regulators of m6A modifications in AML could provide further insights into AML biology and uncover more effective therapeutic strategies for patients with AML. Here, we report overexpression of YTHDF1, an m6A reader protein, in human AML samples at the protein level with enrichment in leukemia stem cells (LSC).

Discovery of the hidden coding information in cancers: Mechanisms and biological functions.

Most proteins are derived from the translation of coding sequence (CDS) in messenger RNAs (mRNAs). However, accumulating evidence has revealed an unexpected abundance of translation in putative non-coding genomes, especially 5' untranslated region (5' UTR) of mRNAs or non-coding RNA species (ncRNA) such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Notably, many of these UTR- or ncRNA-encoded micropeptides/proteins play important roles in human malignancies.

A novel isoform of hydroxyacyl-CoA dehydrogenase inhibits cell proliferation.

Hydroxyacyl-CoA dehydrogenase (HADH) catalyzes the third reaction of mitochondrial β-oxidation cascade, while the regulation of its expression and function remains to be elucidated. Using the quantitative translation initiation sequencing (QTI-seq), we have identified that murine Hadh mRNA has two alternative translation start codons. We demonstrated that translation from upstream start codon encodes the mitochondrial isoform of HADH, while translation from downstream start codon produces a short isoform (HADH-S) with predominant nuclear localization.

A panel of platelet-associated circulating long non-coding RNAs as potential biomarkers for colorectal cancer.

Evidence has suggested the potential of tumor-educated platelets as a biomarker trove for cancer diagnostics, but the difficulty in isolation limits its application. Since most of the circulating RNAs are derived from platelets, the change of RNA profile in platelets may lead to altered RNA expression in serum. Here, we identified a panel of platelet-associated long non-coding RNAs (lncRNAs) and evaluated its diagnostic capacity in serum of colorectal cancer (CRC) patients.

Ribosome profiling reveals translatome remodeling in cancer cells in response to zinc oxide nanoparticles.

The anticancer effect of zinc oxide nanoparticles (ZnO NPs) largely relies on cellular responses such as alteration of gene expression. Although ZnO NPs have been reported to induce transcriptional changes, the potential of ZnO NPs to affect cellular translatome remains largely unknown. Using ribosome profiling, we demonstrated that the transcription of 78 genes and the translation of 1,448 genes are affected during one hour of ZnO NPs exposure in A549 human lung cancer cells.

Decoding mA mRNA methylation by reader proteins in cancer.

N-methyladenosine (mA), the most prevalent internal modification in eukaryotic mRNAs, regulates gene expression at the post-transcriptional level. The reader proteins of mA, mainly YTH domain-containing proteins, specifically recognize mA-modified mRNAs and regulate their metabolism. Recent studies have highlighted essential roles of mA readers in the initiation and development of human cancers.

RNA modifications in cardiovascular diseases, the potential therapeutic targets.

More than one hundred RNA modifications decorate the chemical and topological properties of these ribose nucleotides, thereby executing their biological functions through post-transcriptional regulation. In cardiovascular diseases, a wide range of RNA modifications including mA (N6-adenosine methylation), mC (5-methylcytidin), Nm (2'-O-ribose-methylation), Ψ (pseudouridine), mG (N7-methylguanosine), and mA (N1-adenosine methylation) have been found in tRNA, rRNA, mRNA and other noncoding RNA, which can function as a novel mechanism in metabolic syndrome, heart failure, coronary heart disease, and hypertension. In this review, we will summarize the current understanding of the regulatory roles and significance of several types of RNA modifications in CVDs (cardiovascular diseases) and the interplay between RNA modifications and noncoding RNA, epigenetics.

YTHDF1-regulated expression of TEAD1 contributes to the maintenance of intestinal stem cells.

N6-methyladenosine (mA) mRNA modification has been defined as a crucial regulator in various biological processes. Recent studies indicated an essential role of YTHDF1, an mA reader, in the maintenance of intestinal stem cells (ISCs), while the detailed mechanism remains to be explored. By searching our mA sequencing, RNA sequencing, and ribosome profiling data, we identified the transcriptional enhanced associate domain 1 (TEAD1) as a direct target of YTHDF1.

Myeloid cells protect intestinal epithelial barrier integrity through the angiogenin/plexin-B2 axis.

Communication between myeloid cells and epithelium plays critical role in maintaining intestinal epithelial barrier integrity. Myeloid cells interact with intestinal epithelial cells (IECs) by producing various mediators; however, the molecules mediating their crosstalk remain incompletely understood. Here, we report that deficiency of angiogenin (Ang) in mouse myeloid cells caused impairment of epithelial barrier integrity, leading to high susceptibility to DSS-induced colitis.

YTHDF1-mediated translation amplifies Wnt-driven intestinal stemness.

N6-methyladenosine (m A) mRNA methylation has emerged as an important player in many biological processes by regulating gene expression. However, its roles in intestinal stem cell (ISC) homeostasis remain largely unknown. Here, we report that YTHDF1, an m A reader, is highly expressed in ISCs and its expression is upregulated by Wnt signaling at the translational level.

A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity.

Upon initiation at a start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins. While some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known about how the ribosome normally prevents spontaneous frameshift errors that can have dire consequences if uncorrected. Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3' end of 18S rRNA to scan the AUG-like codons after the decoding process.

The role of ATF3 in ZnO nanoparticle-induced genotoxicity and cytotoxicity in bronchial epithelial cells.

ZnO nanoparticle (ZnO NP) exposure causes oxidative stress in the respiratory system, leading to pulmonary damage. Activating transcription factor 3 (ATF3) participates in a variety of cellular stress responses. However, the role of ATF3 in ZnO NP genotoxicity and cytotoxicity remains to be explored.

Inhibition of RNA polymerase III transcription by Triptolide attenuates colorectal tumorigenesis.

Background: Upregulation of RNA polymerase (Pol) III products, including tRNAs and 5S rRNA, in tumor cells leads to enhanced protein synthesis and tumor formation, making it a potential target for cancer treatment. In this study, we evaluated the inhibition of Pol III transcription by triptolide and the anti-cancer effect of this drug in colorectal tumorigenesis.

Methods: The effect of triptolide on colorectal cancer development was assessed in colorectal cancer mouse models, 3D organoids, and cultured cells.

Autophagic flux blockage in alveolar epithelial cells is essential in silica nanoparticle-induced pulmonary fibrosis.

Silica nanoparticles (SiNPs) have been reported to induce pulmonary fibrosis (PF) with an unknown mechanism. Recently, the activation of autophagy, a lysosome-dependent cell degradation pathway, by SiNPs has been identified in alveolar epithelial cells (AECs). However, the underlying mechanism and the relevance of SiNPs-induced autophagy to the development of PF remain elusive.

The regulatory network of miR-141 in the inhibition of angiogenesis.

The miR-200 family, consisting of miR-200a/b/c, miR-141, and miR-429, is well known to inhibit epithelial-to-mesenchymal transition (EMT) in cancer invasion and metastasis. Among the miR-200 family members, miR-200a/b/c and miR-429 have been reported to inhibit angiogenesis. However, the role of miR-141 in angiogenesis remains elusive, as contradicting results have been found in different cancer types and tumor models.

Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity.

A series of novel fusidic acid (FA) derivatives were synthesized and screened for their in vitro cytotoxicity against the Hela, U87, KBV and MKN45 cancer cell lines. Selected FA derivatives with anti-tumor activity were firstly identified including compound 4, which exhibited good anti-proliferative activity with IC values in the range of 1.26-3.

Silica nanoparticle releases SIRT6-induced epigenetic silencing of follistatin.

Follistatin (FST) plays a protective role during silica nanoparticle (SiO NP) exposure. SiO NP treatment induces FST transcription with an unknown mechanism. We herein reported that SIRT6, one of the sirtuin family members, induced epigenetic silencing of FST.

The emerging role of follistatin under stresses and its implications in diseases.

Follistatin (FST), a single-chain glycosylated protein, is expressed in various tissues. The essential biological function of FST is binding and neutralizing transforming growth factor β (TGF-β) superfamily, including activin, myostatin, and bone morphogenetic protein (BMP). Emerging evidence indicates that FST also serves as a stress responsive protein, which plays a protective role under a variety of stresses.

Angiogenin Prevents Progranulin A9D Mutation-Induced Neuronal-Like Cell Apoptosis Through Cleaving tRNAs into tiRNAs.

Gene defects have been recognized as prominent factors in the etiology and pathogenesis of neurodegeneration. Among 60 neurodegeneration-related mutations in progranulin (PGRN), a mutation in PGRN gene exon 1 introduces a charged amino acid in the hydrophobic core of its signal peptide at residue 9 (named PGRN A9D) and results in incorrect cytoplasmic sorting. However, the pathogenesis of this mutation remains elusive.

Transcriptional activation of follistatin by Nrf2 protects pulmonary epithelial cells against silica nanoparticle-induced oxidative stress.

Silica nanoparticles (SiO2 NPs) cause oxidative stress in respiratory system. Meanwhile, human cells launch adaptive responses to overcome SiO2 NP toxicity. However, besides a few examples, the regulation of SiO2 NP-responsive proteins and their functions in SiO2 NP response remain largely unknown.