Understanding principles of miRNA target recognition and function through integrated biological and bioinformatics approaches

2014 ◽  
Vol 5 (3) ◽  
pp. 361-379 ◽  
Author(s):  
Adam P. Carroll ◽  
Gregory J. Goodall ◽  
Bing Liu
Keyword(s):  
Mirna Target ◽  
Target Recognition ◽  
And Function

scholarly journals A DDX6-CNOT1 Complex and W-Binding Pockets in CNOT9 Reveal Direct Links between miRNA Target Recognition and Silencing

2014 ◽  
Vol 54 (5) ◽  
pp. 737-750 ◽  
Author(s):  
Ying Chen ◽  
Andreas Boland ◽  
Duygu Kuzuoğlu-Öztürk ◽  
Praveen Bawankar ◽  
Belinda Loh ◽  
...  
Keyword(s):  
Mirna Target ◽  
Target Recognition ◽  
Binding Pockets

Neuronal growth and target recognition: lessons from the leech

2001 ◽  
Vol 79 (2) ◽  
pp. 204-217 ◽  
Author(s):  
Michael W Baker ◽  
Eduardo R Macagno
Keyword(s):  
Nervous System ◽  
Target Recognition ◽  
Structure And Function ◽  
Neuronal Structure ◽  
Peripheral Neurons ◽  
Unique System ◽  
Molecular Studies ◽  
The Subject ◽  
The 1960S ◽  
And Function

The nervous system of the leech has been the subject of numerous studies since its "rediscovery" in the 1960s as a unique system for the study of the properties of glial cells. Subsequently, anatomical, physiological, and embryological studies of identified neurons have yielded a wealth of information about the differentiation of neuronal structure and function. In recent years, cellular approaches to the development of identified central and peripheral neurons have been complemented by molecular studies that promise to reveal the mechanisms by which neurons form their complex arbors and innervate specific targets.

scholarly journals Both microRNA-455-5p and -3p repress hypoxia-inducible factor-2α expression and coordinately regulate cartilage homeostasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yoshiaki Ito ◽  
Tokio Matsuzaki ◽  
Fumiaki Ayabe ◽  
Sho Mokuda ◽  
Ryota Kurimoto ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mirna Target ◽  
Hypoxia Inducible Factor ◽  
Cartilage Degeneration ◽  
Joint Disease ◽  
Cartilage Homeostasis ◽  
Elevated Expression ◽  
A Cell ◽  
Target Screening ◽  
And Function

AbstractOsteoarthritis (OA), the most common aging-related joint disease, is caused by an imbalance between extracellular matrix synthesis and degradation. Here, we discover that both strands of microRNA-455 (miR-455), -5p and -3p, are up-regulated by Sox9, an essential transcription factor for cartilage differentiation and function. Both miR-455-5p and -3p are highly expressed in human chondrocytes from normal articular cartilage and in mouse primary chondrocytes. We generate miR-455 knockout mice, and find that cartilage degeneration mimicking OA and elevated expression of cartilage degeneration-related genes are observed at 6-months-old. Using a cell-based miRNA target screening system, we identify hypoxia-inducible factor-2α (HIF-2α), a catabolic factor for cartilage homeostasis, as a direct target of both miR-455-5p and -3p. In addition, overexpression of both miR-455-5p and -3p protect cartilage degeneration in a mouse OA model, demonstrating their potential therapeutic value. Furthermore, knockdown of HIF-2α in 6-month-old miR-455 knockout cartilage rescues the elevated expression of cartilage degeneration-related genes. These data demonstrate that both strands of a miRNA target the same gene to regulate articular cartilage homeostasis.

scholarly journals Beyond the seed: structural basis for supplementary microRNA targeting

2018 ◽  
Author(s):  
Jessica Sheu-Gruttadauria ◽  
Yao Xiao ◽  
Luca F. R. Gebert ◽  
Ian J. MacRae
Keyword(s):  
Mirna Target ◽  
Target Recognition ◽  
Structural Basis ◽  
Seed Region ◽  
Base Pairs ◽  
Argonaute Proteins ◽  
Target Rna ◽  
Mirna Seed ◽  
Mirna Targeting

AbstractmicroRNAs (miRNA) guide Argonaute proteins to mRNAs targeted for repression. Target recognition occurs primarily through the miRNA seed region, composed of guide (g) nucleotides g2–g8. However, nucleotides beyond the seed are also important for some known miRNA-target interactions. Here, we report the structure of human Argonaute2 (Ago2) engaged with a target RNA recognized through both miRNA seed and supplementary (g13–g16) regions. Ago2 creates a “supplementary chamber” that accommodates up to 5 miRNA-target base pairs. Seed and supplementary chambers are adjacent to each other, and can be bridged by an unstructured target loop of 1–15 nucleotides. Opening of the supplementary chamber may be constrained by tension in the miRNA 3' tail as increases in miRNA length stabilize supplementary interactions. Contrary to previous reports, we demonstrate optimal supplementary interactions can increase target affinity >20-fold. These results provide a mechanism for extended miRNA-targeting, suggest a function for 3' isomiRs in tuning miRNA targeting specificity, and indicate that supplementary interactions may contribute more to target recognition than is widely appreciated.

scholarly journals Global identification of functional microRNA::mRNA interactions in Drosophila

2018 ◽  
Author(s):  
Hans-Hermann Wessels ◽  
Svetlana Lebedeva ◽  
Antje Hirsekorn ◽  
Neelanjan Mukherjee ◽  
Uwe Ohler
Keyword(s):  
Mirna Target ◽  
Signal To Noise Ratio ◽  
Absolute Quantification ◽  
Mediated Effects ◽  
Target Sites ◽  
Experimental Annotation ◽  
Global Identification ◽  
And Function

AbstractMicroRNAs (miRNAs) are key mediators of post-transcriptional gene expression silencing. Although Drosophila has been of critical importance for miRNA discovery, biogenesis and function, there has been no comprehensive experimental annotation of functional miRNA target sites. To close this gap, we generated the first in vivo map of miRNA::mRNA interactions in Drosophila melanogaster, making use of crosslinked nucleotides in Argonaute (AGO) crosslinking and immunoprecipitation (CLIP) experiments that enable an unambiguous assignment of miRNAs to AGO binding sites at much higher signal-to-noise ratio than computational predictions alone.Absolute quantification of cellular miRNA levels showed the miRNA pool in Drosophila cell lines to be more diverse than previously reported. Benchmarking two different CLIP approaches, we identified a similar predictive potential to unambiguously assign thousands of miRNA::mRNA pairs from AGO1 interaction data at unprecedented depth. Quantitative RNA-Seq and subcodon-resolution ribosomal footprinting data upon AGO1 depletion enabled the determination of miRNA-mediated effects on target expression and translation. We thus provide the first comprehensive resource of miRNA target sites as well as their quantitative functional impact in Drosophila.

scholarly journals tRForest: a novel random forest-based algorithm for tRNA-derived fragment target prediction

2021 ◽  
Author(s):  
Rohan Parikh ◽  
Briana Wilson ◽  
Laine Marrah ◽  
Zhangli Su ◽  
Shekhar Saha ◽  
...  
Keyword(s):  
Random Forest ◽  
Small Rnas ◽  
Mirna Target ◽  
Learning Algorithm ◽  
Target Prediction ◽  
Mirna Target Prediction ◽  
Gene Ontology Analysis ◽  
Neuronal Function ◽  
Expression Of Genes ◽  
And Function

tRNA fragments (tRFs) are small RNAs comparable to the size and function of miRNAs. tRFs are generally Dicer independent, are found associated with Ago, and can repress expression of genes post-transcriptionally. Given that this expands the repertoire of small RNAs capable of post-transcriptional gene expression, it is important to predict tRF targets with confidence. Some attempts have been made to predict tRF targets, but are limited in the scope of tRF classes used in prediction or limited in feature selection. We hypothesized that established miRNA target prediction features applied to tRFs through a random forest machine learning algorithm will immensely improve tRF target prediction. Using this approach, we show significant improvements in tRF target prediction for all classes of tRFs and validate our predictions in two independent cell lines. Finally, Gene Ontology analysis suggests that among the tRFs conserved between mice and humans, the predicted targets are enriched significantly in neuronal function, and we show this specifically for tRF-3009a. These improvements to tRF target prediction further our understanding of tRF function broadly across species and provide avenues for testing novel roles for tRFs in biology. We have created a publicly available website for the targets of tRFs predicted by tRForest.

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