Origin, evolution and diversification of plant ARGONAUTE proteins

MicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and generate primary transcripts that are processed by RNase III-endonucleases DROSHA and DICER into small RNAs of approximately 21 nucleotides. All miRNAs are loaded into Argonaute proteins in the RNA-induced silencing complex (RISC) and act as post-transcriptional regulators by binding to the 3′- untranslated region (UTR) of mRNAs. This seed-dependent miRNA binding inhibits the translation and/or promotes the degradation of mRNA targets. Surprisingly, recent data presents evidence for a target-mediated decay mechanism that controls the level of specific miRNAs. In addition, several non-canonical miRNA-containing genes have been recently described and unexpected functions of miRNAs have been identified. For instance, several miRNAs are located in the nucleus, where they are involved in the transcriptional activation or silencing of target genes. These epigenetic modifiers are recruited by RISC and guided by miRNAs to specific loci in the genome. Here, we will review non-canonical aspects of miRNA biology, including novel regulators of miRNA expression and functions of miRNAs in the nucleus.

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Protease-mediated processing of Argonaute proteins controls small RNA association

Molecular Cell ◽

10.1016/j.molcel.2021.03.029 ◽

2021 ◽

Author(s):

Rajani Kanth Gudipati ◽

Kathrin Braun ◽

Foivos Gypas ◽

Daniel Hess ◽

Jan Schreier ◽

...

Keyword(s):

Small Rna ◽

Argonaute Proteins

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Argonaute proteins: Structural features, functions and emerging roles

Journal of Advanced Research ◽

10.1016/j.jare.2020.04.017 ◽

2020 ◽

Vol 24 ◽

pp. 317-324 ◽

Cited By ~ 2

Author(s):

Jin'en Wu ◽

Jing Yang ◽

William C. Cho ◽

Yadong Zheng

Keyword(s):

Structural Features ◽

Argonaute Proteins

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The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins

RNA ◽

10.1261/rna.1606309 ◽

2009 ◽

Vol 15 (6) ◽

pp. 1059-1066 ◽

Cited By ~ 91

Author(s):

D. Lazzaretti ◽

I. Tournier ◽

E. Izaurralde

Keyword(s):

Argonaute Proteins ◽

Terminal Domains

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AGOPredict: A Predictor for Identifying Argonaute Proteins

10.1109/icisce50968.2020.00048 ◽

2020 ◽

Author(s):

Shanshan Yang ◽

Jinjin Long ◽

Heng Chen ◽

Bifang He

Keyword(s):

Argonaute Proteins

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Imaging the Cellular Dynamics of Drosophila Argonaute Proteins

Methods in Molecular Biology - Argonaute Proteins ◽

10.1007/978-1-61779-046-1_10 ◽

2011 ◽

pp. 143-159

Author(s):

Jing Li ◽

Nima Najand ◽

Wendy Long ◽

Andrew Simmonds

Keyword(s):

Cellular Dynamics ◽

Argonaute Proteins

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SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2116668118 ◽

2021 ◽

Vol 118 (52) ◽

pp. e2116668118

Author(s):

Paulina Pawlica ◽

Therese A. Yario ◽

Sylvia White ◽

Jianhui Wang ◽

Walter N. Moss ◽

...

Keyword(s):

Small Rna ◽

Leucine Zipper ◽

Health Concern ◽

Interferon Signaling ◽

Basic Leucine Zipper ◽

Argonaute Proteins ◽

Evolutionarily Conserved ◽

Core Components ◽

Cellular Machinery ◽

The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), continues to be a pressing health concern. In this study, we investigated the impact of SARS-CoV-2 infection on host microRNA (miRNA) populations in three human lung-derived cell lines, as well as in nasopharyngeal swabs from SARS-CoV-2–infected individuals. We did not detect any major and consistent differences in host miRNA levels after SARS-CoV-2 infection. However, we unexpectedly discovered a viral miRNA-like small RNA, named CoV2-miR-O7a (for SARS-CoV-2 miRNA-like ORF7a-derived small RNA). Its abundance ranges from low to moderate as compared to host miRNAs and it associates with Argonaute proteins—core components of the RNA interference pathway. We identify putative targets for CoV2-miR-O7a, including Basic Leucine Zipper ATF-Like Transcription Factor 2 (BATF2), which participates in interferon signaling. We demonstrate that CoV2-miR-O7a production relies on cellular machinery, yet is independent of Drosha protein, and is enhanced by the presence of a strong and evolutionarily conserved hairpin formed within the ORF7a sequence.

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Skipping and sliding to optimize target search on protein-bound DNA and RNA

10.1101/2020.06.04.133629 ◽

2020 ◽

Author(s):

Misha Klein ◽

Tao Ju Cui ◽

Ian MacRae ◽

Chirlmin Joo ◽

Martin Depken

Keyword(s):

Nucleic Acid ◽

Single Molecule ◽

Diffusion Limit ◽

Optimal Search ◽

Dna And Rna ◽

Argonaute Proteins ◽

Large Pool ◽

Search Speed ◽

Crowded Environments ◽

Acid Substrate

Rapidly finding a specific nucleic-acid sequences in a large pool of competing off-targets is a fundamental challenge overcome by all living systems. To optimize the search and beat the diffusion limit, it is known that searchers should spend time sliding along the nucleic-acid substrate. Still, such sliding generally has to contend with high levels of molecular crowding on the substrate, and it remains unclear what effect this has on optimal search strategies. Using mechanistic modelling informed by single-molecule data, we show how sliding combined with correlated short-ranged skips allow searchers to maintain search speed on densely crowded substrates. We determine the conditions of optimal search, which show that an optimized searchers always spend more than half its time skipping and sliding along the substrate. Applying our theory to single-molecule data, we determine that both human and bacterial Argonaute proteins alternate between sliding 10 nt and skipping 30 nt along the substrate. We show that this combination of skipping and sliding lengths allows the searcher to maintain search speeds largely unaffected by molecular roadblocks covering up to 70% of the substrate. Our novel combination of experimental and theoretical approach could also help elucidate how other systems ensure rapid search in crowded environments.

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MicroRNA Regulation of the Autotaxin-Lysophosphatidic Acid Signaling Axis

Cancers ◽

10.3390/cancers11091369 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1369 ◽

Cited By ~ 3

Author(s):

Mandi M. Murph

Keyword(s):

Lysophosphatidic Acid ◽

Current Status ◽

Mirna Regulation ◽

Exciting Field ◽

Microrna Regulation ◽

Normal Tissues ◽

Argonaute Proteins ◽

Signaling Axis ◽

Lysophosphatidic Acid Signaling ◽

Lysophosphatidic Acid Receptors

The revelation that microRNAs (miRNAs) exist within the human genome uncovered an underappreciated mechanism of gene expression. For cells to regulate expression of their genes, miRNA molecules and argonaute proteins bind to mRNAs and interfere with efficient translation of the RNA transcript. Although miRNAs have important roles in normal tissues, miRNAs may adopt aberrant functions in malignant cells depending on their classification as either a tumor suppressor or oncogenic miRNA. Within this review, the current status of miRNA regulation is described in the context of signaling through the lysophosphatidic acid receptors, including the lysophosphatidic acid-producing enzyme, autotaxin. Thus far, research has revealed miRNAs that increase in response to lysophosphatidic acid stimulation, such as miR-21, miR-30c-2-3p, and miR-122. Other miRNAs inhibit the translation of lysophosphatidic acid receptors, such as miR-15b, miR-23a, and miR200c, or proteins that are downstream of lysophosphatidic acid signaling, such as miR-146 and miR-21. With thousands of miRNAs still uncharacterized, it is anticipated that the complex regulation of lysophosphatidic acid signaling by miRNAs will continue to be elucidated. RNA-based therapeutics have entered the clinic with enormous potential in precision medicine. This exciting field is rapidly emerging and it will be fascinating to witness its expansion in scope.

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