The Etiological Agent of Lyme Disease, Borrelia burgdorferi, Appears To Contain Only a Few Small RNA Molecules

ABSTRACT Small regulatory RNAs (sRNAs) have recently been shown to be the main controllers of several regulatory pathways. The function of sRNAs depends in many cases on the RNA-binding protein Hfq, especially for sRNAs with an antisense function. In this study, the genome of Borrelia burgdorferi was subjected to different searches for sRNAs, including direct homology and comparative genomics searches and ortholog- and annotation-based search strategies. Two new sRNAs were found, one of which showed complementarity to the rpoS region, which it possibly controls by an antisense mechanism. The role of the other sRNA is unknown, although observed complementarities against particular mRNA sequences suggest an antisense mechanism. We suggest that the low level of sRNAs observed in B. burgdorferi is at least partly due to the presumed lack of both functional Hfq protein and RNase E activity.

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Stem-loops direct precise processing of 3′ UTR-derived small RNA MicL

10.1101/341578 ◽

2018 ◽

Author(s):

Taylor B Updegrove ◽

Andrew B Kouse ◽

Katarzyna J Bandyra ◽

Gisela Storz

Keyword(s):

Small Rna ◽

Cleavage Site ◽

Differential Sensitivity ◽

Rnase E ◽

Small Regulatory Rnas ◽

Regulatory Rnas ◽

Derivatives Of

AbstractIncreasing numbers of 3′UTR-derived small, regulatory RNAs (sRNAs) are being discovered in bacteria, most generated by cleavage from longer transcripts. The enzyme required for these cleavages has been reported to be RNase E, the major endoribonuclease in enterica bacteria. Previous studies investigating RNase E have come to a range of different conclusions regarding the determinants for RNase E processing. To understand the sequence and structure determinants for the precise processing of the 3′ UTR-derived sRNAs, we examined the cleavage of multiple mutant and chimeric derivatives of the 3′ UTR-derived MicL sRNA in vivo and in vitro. Our results revealed that tandem stem-loops 3′ to the cleavage site define optimal, correctly-positioned cleavage of MicL and likely other similar sRNAs. Moreover, our assays of MicL, ArcZ and CpxQ showed that sRNAs exhibit differential sensitivity to RNase E, likely a consequence of a hierarchy of sRNA features recognized by the endonuclease.

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Mechanistic insights into small RNA recognition and modification by the HEN1 methyltransferase

Biochemical Journal ◽

10.1042/bj20121699 ◽

2013 ◽

Vol 453 (2) ◽

pp. 281-290 ◽

Cited By ~ 8

Author(s):

Alexandra Plotnikova ◽

Simona Baranauskė ◽

Aleksandr Osipenko ◽

Saulius Klimašauskas ◽

Giedrius Vilkaitis

Keyword(s):

Small Rna ◽

Rna Binding ◽

Kinetic Studies ◽

Rna Recognition ◽

Dependent Manner ◽

Single Turnover ◽

Small Regulatory Rnas ◽

Regulatory Rnas ◽

Isotope Partitioning ◽

Kinetics Of

The HEN1 methyltransferase from Arabidopsis thaliana modifies the 3′-terminal nucleotides of small regulatory RNAs. Although it is one of the best characterized members of the 2′-O-methyltransferase family, many aspects of its interactions with the cofactor and substrate RNA remained unresolved. To better understand the substrate interactions and contributions of individual steps during HEN1 catalysis, we studied the binding and methylation kinetics of the enzyme using a series of unmethylated, hemimethylated and doubly methylated miRNA and siRNA substrates. The present study shows that HEN1 specifically binds double-stranded unmethylated or hemimethylated miR173/miR173* substrates with a subnanomolar affinity in a cofactor-dependent manner. Kinetic studies under single turnover and pre-steady state conditions in combination with isotope partitioning analysis showed that the binary HEN1–miRNA/miRNA* complex is catalytically competent; however, successive methylation of the two strands in a RNA duplex occurs in a non-processive (distributive) manner. We also find that the observed moderate methylation strand preference is largely exerted at the RNA-binding step and is fairly independent of the nature of the 3′-terminal nucleobase, but shows some dependency on proximal nucleotide mispairs. The results of the present study thus provide novel insights into the mechanism of RNA recognition and modification by a representative small RNA 2′-O-methyltransferase.

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Investigating the Underlying Mechanisms of Circular RNAs and Their Application in Clinical Research of Cervical Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.653051 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jian Liu ◽

He Zhu ◽

Li Fu ◽

Tianmin Xu

Keyword(s):

Cervical Cancer ◽

Rna Binding ◽

Regulation Of Gene Expression ◽

Rna Binding Protein ◽

Circular Rnas ◽

Rna Molecules ◽

Innovative Strategies ◽

Non Coding Rna ◽

Underlying Mechanisms

Circular RNAs (circRNAs) are non-coding RNA molecules, and these are differentially expressed in various diseases, including cancer, suggesting that circRNAs can regulate certain diseases. CircRNAs can act as miRNAs sponges, RNA-binding protein (RBP) sponges, and translation regulators, and they can become an important part of the regulation of gene expression. Furthermore, because of their biomedical features in body fluids, such as high abundance, conservation, and stability, circRNAs are seen as potential biomarkers for various cancers. Cervical cancer (CC) is one of the main causes of cancer-related death in women, and there have been a large number of studies that analyze circRNAs as a new object to be evaluated in CC. Therefore, this review, by understanding the role of circRNAs in CC, may create innovative strategies in the future clinical diagnosis, treatment, and prognosis of CC and promote the development of personalized and highly accurate cancer therapy.

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Smooth muscle-specific HuR knockout induces defective autophagy and atherosclerosis

Cell Death and Disease ◽

10.1038/s41419-021-03671-2 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Shanshan Liu ◽

Xiuxin Jiang ◽

Xiuru Cui ◽

Jingjing Wang ◽

Shangming Liu ◽

...

Keyword(s):

Smooth Muscle ◽

Cardiovascular Events ◽

Rna Binding ◽

Rna Binding Protein ◽

Plaque Burden ◽

Atherosclerotic Plaques ◽

Ampk Activation ◽

Homeostatic Regulation ◽

Human Antigen R

AbstractHuman antigen R (HuR) is a widespread RNA-binding protein involved in homeostatic regulation and pathological processes in many diseases. Atherosclerosis is the leading cause of cardiovascular disease and acute cardiovascular events. However, the role of HuR in atherosclerosis remains unknown. In this study, mice with smooth muscle-specific HuR knockout (HuRSMKO) were generated to investigate the role of HuR in atherosclerosis. HuR expression was reduced in atherosclerotic plaques. As compared with controls, HuRSMKO mice showed increased plaque burden in the atherosclerotic model. Mechanically, HuR could bind to the mRNAs of adenosine 5′-monophosphate-activated protein kinase (AMPK) α1 and AMPKα2, thus increasing their stability and translation. HuR deficiency reduced p-AMPK and LC3II levels and increased p62 level, thereby resulting in defective autophagy. Finally, pharmacological AMPK activation induced autophagy and suppressed atherosclerosis in HuRSMKO mice. Our findings suggest that smooth muscle HuR has a protective effect against atherosclerosis by increasing AMPK-mediated autophagy.

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Extensive Analysis of miRNA Trimming and Tailing Indicates that AGO1 Has a Complex Role in miRNA Turnover

Plants ◽

10.3390/plants10020267 ◽

2021 ◽

Vol 10 (2) ◽

pp. 267

Author(s):

Axel J. Giudicatti ◽

Ariel H. Tomassi ◽

Pablo A. Manavella ◽

Agustin L. Arce

Keyword(s):

Small Rna ◽

Stress Responses ◽

Cellular Localization ◽

Mirna Biogenesis ◽

Small Rna Sequencing ◽

Sequencing Data ◽

Extensive Analysis ◽

Small Regulatory Rnas ◽

Regulatory Rnas ◽

Argonaute 1

MicroRNAs are small regulatory RNAs involved in several processes in plants ranging from development and stress responses to defense against pathogens. In order to accomplish their molecular functions, miRNAs are methylated and loaded into one ARGONAUTE (AGO) protein, commonly known as AGO1, to stabilize and protect the molecule and to assemble a functional RNA-induced silencing complex (RISC). A specific machinery controls miRNA turnover to ensure the silencing release of targeted-genes in given circumstances. The trimming and tailing of miRNAs are fundamental modifications related to their turnover and, hence, to their action. In order to gain a better understanding of these modifications, we analyzed Arabidopsis thaliana small RNA sequencing data from a diversity of mutants, related to miRNA biogenesis, action, and turnover, and from different cellular fractions and immunoprecipitations. Besides confirming the effects of known players in these pathways, we found increased trimming and tailing in miRNA biogenesis mutants. More importantly, our analysis allowed us to reveal the importance of ARGONAUTE 1 (AGO1) loading, slicing activity, and cellular localization in trimming and tailing of miRNAs.

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Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin

FEBS Open Bio ◽

10.1002/2211-5463.12541 ◽

2018 ◽

Vol 8 (12) ◽

pp. 1964-1976 ◽

Cited By ~ 1

Author(s):

Nirmala Tilija Pun ◽

Amrita Khakurel ◽

Aastha Shrestha ◽

Sang‐Hyun Kim ◽

Pil‐Hoon Park

Keyword(s):

Cell Growth ◽

Cancer Cell ◽

Rna Binding ◽

Binding Protein ◽

Critical Role ◽

Rna Binding Protein ◽

Cancer Cell Growth ◽

Globular Adiponectin

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The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases

Biochemical Society Transactions ◽

10.1042/bst20160166 ◽

2016 ◽

Vol 44 (5) ◽

pp. 1321-1337 ◽

Cited By ~ 39

Author(s):

Andrew R. Clark ◽

Jonathan L.E. Dean

Keyword(s):

Inflammatory Mediators ◽

Knockout Mouse ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Human Orthologue ◽

And Function ◽

Detailed Picture ◽

Lines Of Evidence

Twenty years ago, the first description of a tristetraprolin (TTP) knockout mouse highlighted the fundamental role of TTP in the restraint of inflammation. Since then, work from several groups has generated a detailed picture of the expression and function of TTP. It is a sequence-specific RNA-binding protein that orchestrates the deadenylation and degradation of several mRNAs encoding inflammatory mediators. It is very extensively post-translationally modified, with more than 30 phosphorylations that are supported by at least two independent lines of evidence. The phosphorylation of two particular residues, serines 52 and 178 of mouse TTP (serines 60 and 186 of the human orthologue), has profound effects on the expression, function and localisation of TTP. Here, we discuss the control of TTP biology via its phosphorylation and dephosphorylation, with a particular focus on recent advances and on questions that remain unanswered.

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Deficiency of T-Cell Intracellular Antigen 1 in Murine Embryonic Fibroblasts Is Associated with Changes in Mitochondrial Morphology and Respiration

International Journal of Molecular Sciences ◽

10.3390/ijms222312775 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12775

Author(s):

Isabel Carrascoso ◽

Beatriz Ramos Velasco ◽

José M. Izquierdo

Keyword(s):

T Cell ◽

Rna Binding ◽

Mitochondrial Dynamics ◽

Rna Binding Protein ◽

Mitochondrial Morphology ◽

Embryonic Fibroblasts ◽

Intracellular Antigen ◽

Molecular Components ◽

Shed Light

T-cell intracellular antigen 1 (TIA1) is a multifunctional RNA-binding protein involved in regulating gene expression and splicing during development and in response to environmental stress, to maintain cell homeostasis and promote survival. Herein, we used TIA1-deficient murine embryonic fibroblasts (MEFs) to study their role in mitochondria homeostasis. We found that the loss of TIA1 was associated with changes in mitochondrial morphology, promoting the appearance of elongated mitochondria with heterogeneous cristae density and size. The proteomic patterns of TIA1-deficient MEFs were consistent with expression changes in molecular components related to mitochondrial dynamics/organization and respiration. Bioenergetics analysis illustrated that TIA1 deficiency enhances mitochondrial respiration. Overall, our findings shed light on the role of TIA1 in mitochondrial dynamics and highlight a point of crosstalk between potential pro-survival and pro-senescence pathways.

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