scholarly journals RNA modifications modulate gene expression during development

Science ◽  
2018 ◽  
Vol 361 (6409) ◽  
pp. 1346-1349 ◽  
Author(s):  
Michaela Frye ◽  
Bryan T. Harada ◽  
Mikaela Behm ◽  
Chuan He
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Messenger Rna ◽  
Normal Development ◽  
Biological Processes ◽  
Rna Modifications ◽  
Transfer Rnas ◽  
Mrna Metabolism ◽  
Global Protein Synthesis ◽  
And Function

RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programs. They affect diverse eukaryotic biological processes, and the correct deposition of many of these modifications is required for normal development. Messenger RNA (mRNA) modifications regulate various aspects of mRNA metabolism. For example,N6-methyladenosine (m6A) affects the translation and stability of the modified transcripts, thus providing a mechanism to coordinate the regulation of groups of transcripts during cell state maintenance and transition. Similarly, some modifications in transfer RNAs are essential for RNA structure and function. Others are deposited in response to external cues and adapt global protein synthesis and gene-specific translational accordingly and thereby facilitate proper development.

scholarly journals The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Paz Nombela ◽  
Borja Miguel-López ◽  
Sandra Blanco
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Therapeutic Potential ◽  
Biological Processes ◽  
Rna Modifications ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Function ◽  
Made In

AbstractRNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

scholarly journals The crucial roles of N6-methyladenosine (m6A) modification in the carcinogenesis and progression of colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhihao Fang ◽  
Yiqiu Hu ◽  
Jinhui Hu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Regulatory Proteins ◽  
Biological Processes ◽  
The Past ◽  
Common Cancer ◽  
Potential Applications ◽  
Regulated Gene Expression

AbstractAs the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.

scholarly journals Messenger RNA modifications: Form, distribution, and function

Science ◽  
2016 ◽  
Vol 352 (6292) ◽  
pp. 1408-1412 ◽  
Author(s):  
W. V. Gilbert ◽  
T. A. Bell ◽  
C. Schaening
Keyword(s):  
Messenger Rna ◽  
Rna Modifications ◽  
And Function

scholarly journals The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex

2021 ◽  
Author(s):  
Subramaniyam Ravichandran ◽  
Maria Razzaq ◽  
Nazia Parveen ◽  
Ambarnil Ghosh ◽  
Kyeong Kyu Kim
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Biological Significance ◽  
Cellular Functions ◽  
Hairpin Loops ◽  
G Quadruplex ◽  
Reporter Assays ◽  
Expression Activity ◽  
The Stability ◽  
And Function

Abstract G-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1–7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.

scholarly journals A Comprehensive Profile of Mature MicroRNA in the Pig

2017 ◽  
Author(s):  
Xiliang Wang ◽  
David K.C. Cooper ◽  
Zhiming Cai ◽  
Lisha Mou
Keyword(s):  
Gene Expression ◽  
Critical Role ◽  
Mature Mirnas ◽  
Human Diseases ◽  
Meat Production ◽  
Biological Processes ◽  
Non Coding Rna ◽  
Mature Microrna ◽  
And Function ◽  
Posttranscriptional Level

The pig is an important source of meat production and provides a valuable model for certain human diseases. MicroRNA (miRNA), which is non-coding RNA and regulates gene expression at the posttranscriptional level, plays a critical role in various biological processes. Studies on identification and function of mature miRNAs in multiple pig tissues are increasing, yet the literature is limited. Therefore, we reviewed current research to determine the miRNAs expressed in specific pig tissues that are involved in carcass values (including muscle and adipocytes), reproduction (including pituitary, testis, and ovary), and development of some solid organs (e.g., brain, lung, kidney, and liver). We also discuss the possible regulating mechanisms of miRNA. Finally, as pig organs are suitable candidates for xenotransplantation, biomarkers of their miRNA in xenotransplantation were evaluated.

scholarly journals Rapid and dynamic transcriptome regulation by RNA editing and RNA modifications

2016 ◽  
Vol 213 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Konstantin Licht ◽  
Michael F. Jantsch
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Rna Editing ◽  
Messenger Rna ◽  
Gene Expression Regulation ◽  
Rna Modification ◽  
Rna Modifications ◽  
Transcriptome Regulation ◽  
Affect Gene Expression ◽  
Generation Sequencing

Advances in next-generation sequencing and mass spectrometry have revealed widespread messenger RNA modifications and RNA editing, with dramatic effects on mammalian transcriptomes. Factors introducing, deleting, or interpreting specific modifications have been identified, and analogous with epigenetic terminology, have been designated “writers,” “erasers,” and “readers.” Such modifications in the transcriptome are referred to as epitranscriptomic changes and represent a fascinating new layer of gene expression regulation that has only recently been appreciated. Here, we outline how RNA editing and RNA modification can rapidly affect gene expression, making both processes as well suited to respond to cellular stress and to regulate the transcriptome during development or circadian periods.

scholarly journals Expression and Regulation Profile of Mature MicroRNA in the Pig: Relevance to Xenotransplantation

2017 ◽  
Author(s):  
Zongpei Song ◽  
David K. C. Cooper ◽  
Zhiming Cai ◽  
Lisha Mou
Keyword(s):  
Gene Expression ◽  
Critical Role ◽  
Mature Mirnas ◽  
Human Diseases ◽  
Meat Production ◽  
Biological Processes ◽  
Non Coding Rna ◽  
Mature Microrna ◽  
And Function ◽  
Posttranscriptional Level

The pig is an important source of meat production and provides a valuable model for certain human diseases. MicroRNA (miRNA), which is non-coding RNA and regulates gene expression at the posttranscriptional level, plays a critical role in various biological processes. Studies on identification and function of mature miRNAs in multiple pig tissues are increasing, yet the literature is limited. Therefore, we reviewed current research to determine the miRNAs expressed in specific pig tissues that are involved in carcass values (including muscle and adipocytes), reproduction (including pituitary, testis, and ovary), and development of some solid organs (e.g., brain, lung, kidney, and liver). We also discuss the possible regulating mechanisms of miRNA. Finally, as pig organs are suitable candidates for xenotransplantation, biomarkers of their miRNA in xenotransplantation were evaluated.

scholarly journals Platelet gene expression and function in patients with COVID-19

Blood ◽  
2020 ◽  
Vol 136 (11) ◽  
pp. 1317-1329 ◽  
Author(s):  
Bhanu Kanth Manne ◽  
Frederik Denorme ◽  
Elizabeth A. Middleton ◽  
Irina Portier ◽  
Jesse W. Rowley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Mapk Pathway ◽  
Functional Responses ◽  
Protein Ubiquitination ◽  
Healthy Donors ◽  
Pathway Activation ◽  
Increased Risk ◽  
Intravascular Coagulopathy ◽  
And Function

Abstract There is an urgent need to understand the pathogenesis of coronavirus disease 2019 (COVID-19). In particular, thrombotic complications in patients with COVID-19 are common and contribute to organ failure and mortality. Patients with severe COVID-19 present with hemostatic abnormalities that mimic disseminated intravascular coagulopathy associated with sepsis, with the major difference being increased risk of thrombosis rather than bleeding. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters platelet function to contribute to the pathophysiology of COVID-19 remains unknown. In this study, we report altered platelet gene expression and functional responses in patients infected with SARS-CoV-2. RNA sequencing demonstrated distinct changes in the gene-expression profile of circulating platelets of COVID-19 patients. Pathway analysis revealed differential gene-expression changes in pathways associated with protein ubiquitination, antigen presentation, and mitochondrial dysfunction. The receptor for SARS-CoV-2 binding, angiotensin-converting enzyme 2 (ACE2), was not detected by messenger RNA (mRNA) or protein in platelets. Surprisingly, mRNA from the SARS-CoV-2 N1 gene was detected in platelets from 2 of 25 COVID-19 patients, suggesting that platelets may take-up SARS-COV-2 mRNA independent of ACE2. Resting platelets from COVID-19 patients had increased P-selectin expression basally and upon activation. Circulating platelet-neutrophil, -monocyte, and -T-cell aggregates were all significantly elevated in COVID-19 patients compared with healthy donors. Furthermore, platelets from COVID-19 patients aggregated faster and showed increased spreading on both fibrinogen and collagen. The increase in platelet activation and aggregation could partially be attributed to increased MAPK pathway activation and thromboxane generation. These findings demonstrate that SARS-CoV-2 infection is associated with platelet hyperreactivity, which may contribute to COVID-19 pathophysiology.

scholarly journals Mitochondrial MiRNA in Cardiovascular Function and Disease

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1475 ◽  
Author(s):  
Rui Song ◽  
Xiang-Qun Hu ◽  
Lubo Zhang
Keyword(s):  
Gene Expression ◽  
Cardiovascular Diseases ◽  
Mitochondrial Gene ◽  
Mitochondrial Protein ◽  
Cardiovascular Function ◽  
Biological Processes ◽  
Cardiovascular Development ◽  
Small Noncoding Rnas ◽  
Translational Activity ◽  
And Function

MicroRNAs (miRNAs) are small noncoding RNAs functioning as crucial post-transcriptional regulators of gene expression involved in cardiovascular development and health. Recently, mitochondrial miRNAs (mitomiRs) have been shown to modulate the translational activity of the mitochondrial genome and regulating mitochondrial protein expression and function. Although mitochondria have been verified to be essential for the development and as a therapeutic target for cardiovascular diseases, we are just beginning to understand the roles of mitomiRs in the regulation of crucial biological processes, including energy metabolism, oxidative stress, inflammation, and apoptosis. In this review, we summarize recent findings regarding how mitomiRs impact on mitochondrial gene expression and mitochondrial function, which may help us better understand the contribution of mitomiRs to both the regulation of cardiovascular function under physiological conditions and the pathogenesis of cardiovascular diseases.

scholarly journals Base-resolution mapping reveals distinct m1A methylome in nuclear- and mitochondrial-encoded transcripts

2017 ◽  
Author(s):  
Xiaoyu Li ◽  
Xushen Xiong ◽  
Meiling Zhang ◽  
Kun Wang ◽  
Ying Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reverse Transcription ◽  
Translation Efficiency ◽  
Rna Modifications ◽  
Precise Location ◽  
Human Transcriptome ◽  
Functional Studies ◽  
Resolution Mapping ◽  
And Function ◽  
First Time

SUMMARYGene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1-methyladenosine (m1A) is a recently identified mRNA modification; however, little is known about its precise location, regulation and function. Here, we develop a base-resolution m1A profiling method, based on m1A-induced misincorporation during reverse transcription, and report distinct classes of m1A methylome in the human transcriptome. m1A in 5’-UTR, particularly those at the first nucleotide of mRNA, associate with increased translation efficiency. A different subset of m1A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome and are dependent on the methyltransferase TRMT6/61A. Additionally, we show for the first time that m1A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1A level via TRMT61B, a mitochondria-localizing m1A methyltransferase, demonstrates that m1A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1A methylome and provide a resource for functional studies of m1A-mediated epitranscriptomic regulation.

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