Correction to: Seq’ing identity and function in a repeat-derived noncoding RNA world

miR-29b2 and miR-29c play a suppressive role in breast cancer progression. C1orf132 (also named MIR29B2CHG) is the host gene for generating both microRNAs. However, the region also expresses longer transcripts with unknown functions. We employed bioinformatics and experimental approaches to decipher C1orf132 expression and function in breast cancer tissues. We also used the CRISPR/Cas9 technique to excise a predicted C1orf132 distal promoter and followed the behavior of the edited cells by real-time PCR, flow cytometry, migration assay, and RNA-seq techniques. We observed that C1orf132 long transcript is significantly downregulated in triple-negative breast cancer. We also identified a promoter for the longer transcripts of C1orf132 whose functionality was demonstrated by transfecting MCF7 cells with a C1orf132 promoter-GFP construct. Knocking-out the promoter by means of CRISPR/Cas9 revealed no alterations in the expression of the neighboring genes CD46 and CD34, while the expression of miR-29c was reduced by half. Furthermore, the promoter knockout elevated the migration ability of the edited cells. RNA sequencing revealed many up- and downregulated genes involved in various cellular pathways, including epithelial to mesenchymal transition and mammary gland development pathways. Altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell migration.

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The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum

Cell Death and Differentiation ◽

10.1038/s41418-021-00774-3 ◽

2021 ◽

Author(s):

Fei Wang ◽

Qianqian Wang ◽

Baowei Liu ◽

Lisheng Mei ◽

Sisi Ma ◽

...

Keyword(s):

Noncoding Rna ◽

Cerebellar Atrophy ◽

Synaptic Activity ◽

Motor Dysfunction ◽

Cerebellar Development ◽

Full Spectrum ◽

Density Reduction ◽

Adult Mice ◽

Synapse Density ◽

And Function

AbstractThe brain is known to express many long noncoding RNAs (lncRNAs); however, whether and how these lncRNAs function in modulating synaptic stability remains unclear. Here, we report a cerebellum highly expressed lncRNA, Synage, regulating synaptic stability via at least two mechanisms. One is through the function of Synage as a sponge for the microRNA miR-325-3p, to regulate expression of the known cerebellar synapse organizer Cbln1. The other function is to serve as a scaffold for organizing the assembly of the LRP1-HSP90AA1-PSD-95 complex in PF-PC synapses. Although somewhat divergent in its mature mRNA sequence, the locus encoding Synage is positioned adjacent to the Cbln1 loci in mouse, rhesus macaque, and human, and Synage is highly expressed in the cerebella of all three species. Synage deletion causes a full-spectrum cerebellar ablation phenotype that proceeds from cerebellar atrophy, through neuron loss, on to synapse density reduction, synaptic vesicle loss, and finally to a reduction in synaptic activity during cerebellar development; these deficits are accompanied by motor dysfunction in adult mice, which can be rescued by AAV-mediated Synage overexpression from birth. Thus, our study demonstrates roles for the lncRNA Synage in regulating synaptic stability and function during cerebellar development.

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Coding and Noncoding RNA: An Expanding RNA World

Science Signaling ◽

10.1126/stke.2002.133.eg7 ◽

2002 ◽

Vol 2002 (133) ◽

pp. eg7-eg7

Author(s):

L. D. Chong ◽

L. B. Ray ◽

N. R. Gough

Keyword(s):

Noncoding Rna ◽

Rna World

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Structural basis for recognition of human 7SK long noncoding RNA by the La-related protein Larp7

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1806276115 ◽

2018 ◽

Vol 115 (28) ◽

pp. E6457-E6466 ◽

Cited By ~ 20

Author(s):

Catherine D. Eichhorn ◽

Yuan Yang ◽

Lucas Repeta ◽

Juli Feigon

Keyword(s):

Noncoding Rna ◽

Rna Binding ◽

Rna Binding Proteins ◽

Transcription Elongation ◽

Structural Basis ◽

Titration Calorimetry ◽

Rna Recognition Motif ◽

Related Protein ◽

Binding Interface ◽

And Function

The La and the La-related protein (LARP) superfamily is a diverse class of RNA binding proteins involved in RNA processing, folding, and function. Larp7 binds to the abundant long noncoding 7SK RNA and is required for 7SK ribonucleoprotein (RNP) assembly and function. The 7SK RNP sequesters a pool of the positive transcription elongation factor b (P-TEFb) in an inactive state; on release, P-TEFb phosphorylates RNA Polymerase II to stimulate transcription elongation. Despite its essential role in transcription, limited structural information is available for the 7SK RNP, particularly for protein–RNA interactions. Larp7 contains an N-terminal La module that binds UUU-3′OH and a C-terminal atypical RNA recognition motif (xRRM) required for specific binding to 7SK and P-TEFb assembly. Deletion of the xRRM is linked to gastric cancer in humans. We report the 2.2-Å X-ray crystal structure of the human La-related protein group 7 (hLarp7) xRRM bound to the 7SK stem-loop 4, revealing a unique binding interface. Contributions of observed interactions to binding affinity were investigated by mutagenesis and isothermal titration calorimetry. NMR 13C spin relaxation data and comparison of free xRRM, RNA, and xRRM–RNA structures show that the xRRM is preordered to bind a flexible loop 4. Combining structures of the hLarp7 La module and the xRRM–7SK complex presented here, we propose a structural model for Larp7 binding to the 7SK 3′ end and mechanism for 7SK RNP assembly. This work provides insight into how this domain contributes to 7SK recognition and assembly of the core 7SK RNP.

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βlinc1encodes a long noncoding RNA that regulates islet β-cell formation and function

Genes & Development ◽

10.1101/gad.273821.115 ◽

2016 ◽

Vol 30 (5) ◽

pp. 502-507 ◽

Cited By ~ 68

Author(s):

Luis Arnes ◽

Ildem Akerman ◽

Dina A. Balderes ◽

Jorge Ferrer ◽

Lori Sussel

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Cell Formation ◽

Β Cell ◽

And Function

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H19 lncRNA alters methylation and expression of Hnf4α in the liver of metformin-exposed fetuses

Cell Death and Disease ◽

10.1038/cddis.2017.392 ◽

2017 ◽

Vol 8 (12) ◽

pp. e3175-e3175 ◽

Cited By ~ 10

Author(s):

Jie Deng ◽

Martin Mueller ◽

Tingting Geng ◽

Yuanyuan Shen ◽

Ya Liu ◽

...

Keyword(s):

Noncoding Rna ◽

Animal Studies ◽

Fetal Liver ◽

Functional Differentiation ◽

Regulation Of Expression ◽

Adenosylhomocysteine Hydrolase ◽

Human Liver Cell ◽

Key Factor ◽

Mouse Fetuses ◽

And Function

Abstract Metformin is the most widely used anti-diabetic medication worldwide. However, human and animal studies suggest that prenatal metformin exposure may increase the risk of metabolic disorders in adult offspring, yet the underpinning mechanism remains unclear. Here we report that metformin-exposed mouse fetuses exhibit elevated expression of the H19 long noncoding RNA, which induces hypomethylation and increased expression of hepatocyte nuclear factor 4α (HNF4α). As a transcription factor essential for morphological and functional differentiation of hepatocytes, HNF4α also has an indispensable role in the regulation of expression of gluconeogenic genes. Consistently, H19 overexpression in a human liver cell line leads to decreased methylation and increased expression of Hnf4α, with concomitant activation of the gluconeogenic program. Mechanistically, we show that the methylation change of Hnf4α is induced by H19-mediated regulation of S-adenosylhomocysteine hydrolase. We also provide evidence that altered H19 expression is a direct effect of metformin in the fetal liver. Our results suggest that metformin from the mother can directly act upon the fetal liver to modify Hnf4α expression, a key factor for both liver development and function, and that perturbation of this H19/Hnf4α-mediated pathway may contribute to the fetal origin of adult metabolic abnormalities.

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Formation of a Family of Long Intergenic Noncoding RNA Genes with an Embedded Translocation Breakpoint Motif in Human Chromosomal Low Copy Repeats of 22q11.2—Some Surprises and Questions

Non-Coding RNA ◽

10.3390/ncrna4030016 ◽

2018 ◽

Vol 4 (3) ◽

pp. 16 ◽

Cited By ~ 3

Author(s):

Nicholas Delihas

Keyword(s):

Noncoding Rna ◽

Gene Sequence ◽

Translocation Breakpoint ◽

Segmental Duplications ◽

New Genes ◽

Genetic Abnormalities ◽

Low Copy Repeats ◽

Long Intergenic Noncoding Rna ◽

And Function ◽

Rna Genes

A family of long intergenic noncoding RNA (lincRNA) genes, FAM230 is formed via gene sequence duplication, specifically in human chromosomal low copy repeats (LCR) or segmental duplications. This is the first group of lincRNA genes known to be formed by segmental duplications and is consistent with current views of evolution and the creation of new genes via DNA low copy repeats. It appears to be an efficient way to form multiple lincRNA genes. But as these genes are in a critical chromosomal region with respect to the incidence of abnormal translocations and resulting genetic abnormalities, the 22q11.2 region, and also carry a translocation breakpoint motif, several intriguing questions arise concerning the presence and function of the translocation breakpoint sequence in RNA genes situated in LCR22s.

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Human Long Noncoding RNA Interactome: Detection, Characterization and Function

International Journal of Molecular Sciences ◽

10.3390/ijms21031027 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1027 ◽

Cited By ~ 11

Author(s):

Kazimierczyk ◽

Kasprowicz ◽

Kasprzyk ◽

Wrzesinski

Keyword(s):

Noncoding Rna ◽

Potential Role ◽

Integrated Analysis ◽

Biological Functions ◽

Non Coding Rna ◽

Non Coding Rnas ◽

And Function ◽

New Generation ◽

Cellular Components ◽

Proteins And Peptides

The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome "dark matter” belongs to divergent groups of non-coding RNA (ncRNA), that is not translated into proteins. There are two groups of ncRNAs, which include small and long non-coding RNAs (sncRNA and lncRNA respectively). Over the last decade, there has been an increased interest in lncRNAs and their interaction with cellular components. In this review, we presented the newest information about the human lncRNA interactome. The term lncRNA interactome refers to cellular biomolecules, such as nucleic acids, proteins, and peptides that interact with lncRNA. The lncRNA interactome was characterized in the last decade, however, understanding what role the biomolecules associated with lncRNA play and the nature of these interactions will allow us to better understand lncRNA's biological functions in the cell. We also describe a set of methods currently used for the detection of lncRNA interactome components and the analysis of their interactions. We think that such a holistic and integrated analysis of the lncRNA interactome will help to better understand its potential role in the development of organisms and cancers.

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