The long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was initially found to be overexpressed in early non-small cell lung cancer (NSCLC). Accumulating studies have shown that MALAT1 is overexpressed in the tissue or serum of NSCLC and plays a key role in its occurrence and development. In addition, the expression level of MALAT1 is significantly related to the tumor size, stage, metastasis, and distant invasion of NSCLC. Therefore, MALAT1 could be used as a biomarker for the early diagnosis, severity assessment, or prognosis evaluation of NSCLC patients. This review describes the basic properties and biological functions of MALAT1, focuses on the specific molecular mechanism of MALAT1 as a microRNA sponge in the occurrence and development of NSCLC in recent years, and emphasizes the application and potential prospect of MALAT1 in molecular biological markers and targeted therapy of NSCLC.

/pdf/novel-insights-into-malat1-function-as-a-microrna-sponge-in-395sw1epn0.pdf

Novel Insights Into MALAT1 Function as a MicroRNA Sponge in NSCLC

Transfer RNAs with unstable acceptor stems can be tagged by CCA-adding enzymes and targeted for destruction by 3′-5′ exonucleases. The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase] adds CCA to the 3′ ends of transfer RNAs (tRNAs), a critical step in tRNA biogenesis that generates the amino acid attachment site. We found that the CCA-adding enzyme plays a key role in tRNA quality control by selectively marking structurally unstable tRNAs and tRNA-like small RNAs for degradation. Instead of adding CCA to the 3′ ends of these transcripts, CCA-adding enzymes from all three kingdoms of life add CCACCA. In addition, hypomodified mature tRNAs are subjected to CCACCA addition as part of a rapid tRNA decay pathway in vivo. We conjecture that CCACCA addition is a universal mechanism for controlling tRNA levels and preventing errors in translation.

tRNAs Marked with CCACCA Are Targeted for Degradation

Abstract tRNAs are key partners in ribosome-dependent protein synthesis. This process is highly dependent on the fidelity of tRNA aminoacylation by aminoacyl-tRNA synthetases and relies primarily on sets of identities within tRNA molecules composed of determinants and antideterminants preventing mischarging by non-cognate synthetases. Such identity sets were discovered in the tRNAs of a few model organisms, and their properties were generalized as universal identity rules. Since then, the panel of identity elements governing the accuracy of tRNA aminoacylation has expanded considerably, but the increasing number of reported functional idiosyncrasies has led to some confusion. In parallel, the description of other processes involving tRNAs, often well beyond aminoacylation, has progressed considerably, greatly expanding their interactome and uncovering multiple novel identities on the same tRNA molecule. This review highlights key findings on the mechanistics and evolution of tRNA and tRNA-like identities. In addition, new methods and their results for searching sets of multiple identities on a single tRNA are discussed. Taken together, this knowledge shows that a comprehensive understanding of the functional role of individual and collective nucleotide identity sets in tRNA molecules is needed for medical, biotechnological and other applications.

/pdf/the-trna-identity-landscape-for-aminoacylation-and-beyond-1s1jgfip.pdf

The tRNA identity landscape for aminoacylation and beyond

Simple Summary In our journey to fight cancer, biomarkers for prediction and efficacy of therapies could help medical practitioners to give patients the best available treatments in a timely fashion. Non-coding RNA, in most recent times, has been shown to play crucial roles for cancer growth. An exponential increase of evidence in the clinical literature supports their implication to predict patients’ outcomes. In this article, we summarize the current predictive and prognostic value of non-coding RNA in breast cancer. Abstract For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies has shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extraordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer.

/pdf/predictive-and-prognostic-value-of-non-coding-rna-in-breast-1o8mi0sb.pdf

Predictive and Prognostic Value of Non-Coding RNA in Breast Cancer

MALAT1-associated small cytoplasmic RNA (mascRNA) is a highly conserved transfer RNA-like (tRNA-like) noncoding RNA whose function remains largely unknown. We show here that this small RNA molecule played a role in the stringent control of TLR-mediated innate immune responses. mascRNA inhibited activation of NF-κB and mitogen-activated protein kinase (MAPK) signaling and the production of inflammatory cytokines in macrophages stimulated with LPS, a TLR4 ligand. Furthermore, exogenous mascRNA alleviated LPS-induced lung inflammation. However, mascRNA potentiated the phosphorylation of IRF3 and STAT1 and the transcription of IFN-related genes in response to the TLR3 ligand poly(I:C) both in vitro and in vivo. Mechanistically, mascRNA was found to enhance K48-linked ubiquitination and proteasomal degradation of TRAF6, thereby negatively regulating TLR-mediated MyD88-dependent proinflammatory signaling while positively regulating TRIF-dependent IFN signaling. Additionally, heterogeneous nuclear ribonucleoprotein H (hnRNP H) and hnRNP F were found to interact with mascRNA, promote its degradation, and contribute to the fine-tuning of TLR-triggered immune responses. Taken together, our data identify a dual role of mascRNA in both negative and positive regulation of innate immune responses.

/pdf/the-small-rna-mascrna-differentially-regulates-tlr-induced-4nx188mru3.pdf

The small RNA mascRNA differentially regulates TLR-induced proinflammatory and antiviral responses.

mascRNA is a small cytoplasmic RNA derived from the lncRNA MALAT1. After being processed by the tRNA processing enzymes RNase P and RNase Z, mascRNA undergoes CCA addition like tRNAs and folds into a tRNA-like cloverleaf structure. While MALAT1 functions in multiple cellular processes, the role of mascRNA was largely unknown. Here, we show that mascRNA binds directly to the multi-tRNA synthetase complex (MSC) component glutaminyl-tRNA synthetase (QARS). mascRNA promotes global protein translation and cell proliferation by positively regulating QARS protein levels. Our results uncover a role of mascRNA that is independent of MALAT1, but could be part of the molecular mechanism of MALAT1's function in cancer, and provide a paradigm for understanding tRNA-like structures in mammalian cells.

The tRNA-like small noncoding RNA mascRNA promotes global protein translation.

Mitochondria are the main hubs for cellular energy production. Metabolites produced in mitochondria not only feed many important biosynthesis pathways but also function as signaling molecules. Mitochondrial biosynthesis requires collaboration of both nuclear and mitochondrial gene expression systems. In addition, mitochondria have to quickly respond to changes inside and outside the cells and have their own functional states reported to the nucleus and other cellular compartments. The underlying molecular mechanisms of these complex regulations have not been well understood. Recent evidence indicates that in addition to small molecules, non-coding RNAs may contribute to the communication between mitochondria and other cellular compartments and may even serve as signals. In this review, we summarize the current knowledge about mitochondrial non-coding RNAs (including nucleus-encoded non-coding RNAs that are imported into mitochondria and mitochondrion-encoded non-coding RNAs that are exported), their trafficking and their functions in co-regulation of mitochondrial and other cellular processes.

/pdf/non-coding-rna-regulated-cross-talk-between-mitochondria-and-32wejiun8s.pdf

Sipeng Wu

Papers

The tRNA-like small noncoding RNA mascRNA promotes global protein translation.

Non-coding RNA Regulated Cross-Talk Between Mitochondria and Other Cellular Compartments.