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Your search keyword '"Orom, Ulf A."' showing total 12 results
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12 results on '"Orom, Ulf A."'

5. Activating RNAs associate with mediator to enhance chromatin architecture and transcription

Author

Lai, Fan, Orom, Ulf A., Cesaroni, Matteo, Beringer, Malte, Taatjes, Dylan J., Blobel, Gerd A., and Shiekhattar, Ramin

Subjects
RNA -- Properties -- Identification and classification, Cellular signal transduction -- Observations, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms (1-8). Although the functional role for long non-coding [...]

Published
2013
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6. Determination of primary microRNA processing in clinical samples by targeted pri-miR-sequencing

Author

Conrad, Thomas, Ntini, Evgenia, Lang, Benjamin, Cozzuto, Luca, Andersen, Jesper B, Marquardt, Jens U, Ponomarenko, Julia, Tartaglia, Gian Gaetano, Vang Orom, Ulf A, Conrad, Thomas, Ntini, Evgenia, Lang, Benjamin, Cozzuto, Luca, Andersen, Jesper B, Marquardt, Jens U, Ponomarenko, Julia, Tartaglia, Gian Gaetano, and Vang Orom, Ulf A

Abstract

MicroRNA expression is important for gene regulation and deregulated microRNA expression is often observed in disease such as cancer. The processing of primary microRNA transcripts is an important regulatory step in microRNA biogenesis. Due to low expression level and association with chromatin primary microRNAs are challenging to study in clinical samples where input material is limited. Here, we present a high-sensitivity targeted method to determine processing efficiency of several hundred primary microRNAs from total RNA that requires relatively few RNA sequencing reads. We validate the method using RNA from HeLa cells and show the applicability to clinical samples by analyzing RNA from normal liver and hepatocellular carcinoma. We identify 24 primary microRNAs with significant changes in processing efficiency from normal liver to hepatocellular carcinoma, among those the highly expressed miRNA-122 and miRNA-21, demonstrating that differential processing of primary microRNAs is occurring and could be involved in disease. With our method presented here we provide means to study pri-miRNA processing in disease from clinical samples.

Published
2020

8. PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs

Author

Marsico, Annalisa, Huska, Matthew R, Lasserre, Julia, Hu, Haiyang, Vucicevic, Dubravka, Musahl, Anne, Orom, Ulf, and Vingron, Martin

Subjects
Brain Chemistry, mixture model, miRNA transcriptional regulation, Method, Brain, Gene Expression Regulation, Developmental, Molecular Sequence Annotation, Genomics, deepCAGE, Introns, MicroRNAs, Databases, Genetic, Humans, Promoter Regions, Genetic, Algorithms, Transcription Factors
Abstract

The regulation of intragenic miRNAs by their own intronic promoters is one of the open problems of miRNA biogenesis. Here, we describe PROmiRNA, a new approach for miRNA promoter annotation based on a semi-supervised statistical model trained on deepCAGE data and sequence features. We validate our results with existing annotation, PolII occupancy data and read coverage from RNA-seq data. Compared to previous methods PROmiRNA increases the detection rate of intronic promoters by 30%, allowing us to perform a large-scale analysis of their genomic features, as well as elucidate their contribution to tissue-specific regulation. PROmiRNA can be downloaded from http://promirna.molgen.mpg.de.

Published
2013

10. miR-200b mediates post-transcriptional repression of ZFHX1B.

Author

Christoffersen, Nanna Rønbjerg, Silahtaroglu, Asli, Orom, Ulf Andersson, Kauppinen, Sakari, and Lund, Anders H

Abstract

MicroRNAs have important functions during animal development and homeostasis through post-transcriptional regulation of their cognate mRNA targets. ZFHX1B is a transcriptional repressor involved in the TGFbeta signaling pathway and in processes of epithelial to mesenchymal transition via regulation of E-cadherin. We show that Zfhx1b and miR-200b are regionally coexpressed in the adult mouse brain and that miR-200b represses the expression of Zfhx1b via multiple sequence elements present in the 3'-untranslated region. Overexpression of miR-200b leads to repression of endogenous ZFHX1B, and inhibition of miR-200b relieves the repression of ZFHX1B. In accordance with these findings, miR-200b regulates the activity of the E-cadherin promoter.

Published
2007
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11. Molecular mechanisms of long ncRNAs in neurological disorders.

Author

Vučićević D, Schrewe H, and Orom UA

Abstract

Long non-coding RNAs (ncRNAs) have added an unexpected layer of complexity in the regulation of gene expression. Mounting evidence now links long ncRNAs to fundamental biological processes such as development and differentiation, and recent research shows important involvement of long ncRNAs in a variety of diseases including neurodegenerative disorders, such as Parkinson's, Alzheimer's, spinocerebellar ataxia, and Huntington's diseases. Furthermore, long ncRNAs are speculated to be implicated in development of psychiatric disorders such as schizophrenia and bipolar disorders. Long ncRNAs contribute to these disorders in diverse ways, from regulation of transcription to modulation of RNA processing and translation. In this review, we describe the diverse mechanisms reported for long ncRNAs, and discuss how they could mechanistically be involved in the development of neurological disorders.

Published
2014
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12. Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step.

Author

Gumireddy K, Li A, Yan J, Setoyama T, Johannes GJ, Orom UA, Tchou J, Liu Q, Zhang L, Speicher DW, Calin GA, and Huang Q

Subjects
Animals, Female, HEK293 Cells, Humans, Mice, Mice, Inbred NOD, Mice, SCID, Multiprotein Complexes metabolism, Multiprotein Complexes physiology, Protein Binding, RNA, Long Noncoding physiology, Ribonucleoproteins genetics, Ribonucleoproteins isolation & purification, Ribonucleoproteins metabolism, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Neoplasm Metastasis genetics, Protein Biosynthesis genetics, RNA, Long Noncoding metabolism, Ribonucleoproteins physiology
Abstract

Long non-coding RNAs (lncRNAs) are a novel class of regulatory genes that play critical roles in various processes ranging from normal development to human diseases such as cancer progression. Recent studies have shown that lncRNAs regulate the gene expression by chromatin remodelling, transcription, splicing and RNA decay control, enhancer function, and epigenetic regulation. However, little is known about translation regulation by lncRNAs. We identified a translational regulatory lncRNA (treRNA) through genome-wide computational analysis. We found that treRNA is upregulated in paired clinical breast cancer primary and lymph-node metastasis samples, and that its expression stimulates tumour invasion in vitro and metastasis in vivo. Interestingly, we found that treRNA downregulates the expression of the epithelial marker E-cadherin by suppressing the translation of its mRNA. We identified a novel ribonucleoprotein (RNP) complex, consisting of RNA-binding proteins (hnRNP K, FXR1, and FXR2), PUF60 and SF3B3, that is required for this treRNA functions. Translational suppression by treRNA is dependent on the 3'UTR of the E-cadherin mRNA. Taken together, our study indicates a novel mechanism of gene regulation by lncRNAs in cancer progression.

Published
2013
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