RNA processing
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It was long time pressumed that only eukaryotes protect their RNA by 5'-RNA cap. Recently, it was shown that also prokaryotes employ some kind of protection of their RNA in the form of 5'-triphosphate or NAD covalently attached to 5'-terminus. This review discusses the state of art of 5'-RNA cap in eukaryotes and prokaryotes.
- Klíčová slova
- modifikace RNA,
- MeSH
- posttranskripční úpravy RNA MeSH
- RNA čepičky * MeSH
- výzkum MeSH
- Publikační typ
- práce podpořená grantem MeSH
Annals of the New York Academy of Sciences, ISSN 0077-8923 Volume 207, Issue 1, May 1973
492 stran : ilustrace ; 23 cm
Eukaryotic RNA can carry more than 100 different types of chemical modifications. Early studies have been focused on modifications of highly abundant RNA, such as ribosomal RNA and transfer RNA, but recent technical advances have made it possible to also study messenger RNA (mRNA). Subsequently, mRNA modifications, namely methylation, have emerged as key players in eukaryotic gene expression regulation. The most abundant and widely studied internal mRNA modification is N6 -methyladenosine (m6 A), but the list of mRNA chemical modifications continues to grow as fast as interest in this field. Over the past decade, transcriptome-wide studies combined with advanced biochemistry and the discovery of methylation writers, readers, and erasers revealed roles for mRNA methylation in the regulation of nearly every aspect of the mRNA life cycle and in diverse cellular, developmental, and disease processes. Although large parts of mRNA function are linked to its cytoplasmic stability and regulation of its translation, a number of studies have begun to provide evidence for methylation-regulated nuclear processes. In this review, we summarize the recent advances in RNA methylation research and highlight how these new findings have contributed to our understanding of methylation-dependent RNA processing in the nucleus. This article is categorized under: RNA Processing > RNA Editing and Modification RNA Processing > Splicing Regulation/Alternative Splicing RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
Mutations in BRAT1, encoding BRCA1-associated ATM activator 1, have been associated with neurodevelopmental and neurodegenerative disorders characterized by heterogeneous phenotypes with varying levels of clinical severity. However, the underlying molecular mechanisms of disease pathology remain poorly understood. Here, we show that BRAT1 tightly interacts with INTS9/INTS11 subunits of the Integrator complex that processes 3' ends of various noncoding RNAs and pre-mRNAs. We find that Integrator functions are disrupted by BRAT1 deletion. In particular, defects in BRAT1 impede proper 3' end processing of UsnRNAs and snoRNAs, replication-dependent histone pre-mRNA processing, and alter the expression of protein-coding genes. Importantly, impairments in Integrator function are also evident in patient-derived cells from BRAT1 related neurological disease. Collectively, our data suggest that defects in BRAT1 interfere with proper Integrator functions, leading to incorrect expression of RNAs and proteins, resulting in neurodegeneration.
- MeSH
- fenotyp MeSH
- histony MeSH
- jaderné proteiny * genetika MeSH
- lidé MeSH
- mutace MeSH
- neurodegenerativní nemoci * genetika MeSH
- posttranskripční úpravy RNA * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Methods in enzymology ; Vol. 180
600 s. : obr., tab., bibliogr.
Methods in enzymology ; Vol. 181
651 s. : obr., tab., přeruš.bibliogr.
Celogenomové sekvenační analýzy odhalily, že převážná část lidského genomu je transkribována, a identifikovaly tisíce protein nekódujících transkriptů. Nekódující RNA (ncRNA) se dělí na dvě hlavní skupiny: malé a dlouhé ncRNA. Tento přehledový článek je zaměřen na ncRNA s regulační funkcí, a to především na mikroRNA a dlouhé ncRNA. Tyto ncRNA regulují genovou expresi na transkripční a posttranskripční úrovni. V tomto kontextu ncRNA zasahují do regulace většiny buněčných procesů a jejich deregulace má vážné dopady na fenotyp. Již stovky studií prokázaly zapojení ncRNA do patogeneze mnoha onemocnění, od metabolických poruch přes onemocnění orgánových systémů až po různé typy nádorů. Z klinického hlediska patří ncRNA do nové generace diagnostických a prognostických biomarkerů s velkým potenciálem. Vzhledem k vysoké tkáňové specifciitě a schopnosti regulovat více genů často v rámci jedné signální dráhy představují ncRNA i atraktivní terapeutické cíle. Narůstající poznatky o širokém spektru působení ncRNA ukazují na klíčovou roli těchto transkriptů v regulaci exprese. Řada aspektů z biologie ncRNA ještě není objasněna a jejich pochopení nám poskytne nový pohled na komplexnost regulační sítě.
Whole-genome sequencing analyses revealed that the majority of the human genome is transcribed and identified thousands of protein non-coding transcripts. Non-coding RNAs (ncRNAs) are divided into two main groups: small and long ncRNAs. This review is focused on the regulatory ncRNAs mainly on microRNAs and long ncRNAs. These ncRNAs regulate gene expression at the transcriptional and post-transcriptional levels. In this context, ncRNAs are involved in the regulation of most cellular processes and their deregulation has serious impacts on the phenotype. Hundreds of studies have implicated ncRNAs in the pathogenesis of many diseases ranging from metabolic disorders to diseases of organ systems as well as various types of cancers. Clinically, ncRNAs belong to a new generation of diagnostic and prognostic biomarkers with a great potential. Due to high tissue specificity and ability to regulate multiple genes often within one signaling pathway, ncRNAs represent attractive therapeutic targets. Increasing knowledge about a wide spectrum of ncRNA actions demonstrate a pivotal role of these transcripts in expression regulation. Many aspects of the ncRNA biology are still unclear and their understanding will provide us a new perspective on the complexity of the regulatory network.
Biologická terapie, jejímž mechanizmem účinku je použití monoklonálních protilátek proti nějakému proteinu, je používána v klinické praxi již řadu let. V současné době ale vstupují do klinické praxe nové léky ze skupiny biologické terapie, které účinkují na principu RNA-interference. RNA-interference je proces, kterým buňky všech živých organizmů regulují expresi svých genů a při kterém může být zastaven přenos informace o syntéze konkrétního proteinu mezi DNA a ribosomy. Pro terapeutické účely se tohoto efektu dosahuje podáním umělých syntetizovaných oligonukleotidů s přesně danou sekvencí nukleosidů. Jde buď o krátké úseky dvouvláknové RNA, nebo o jednovláknové oligonukleotidy. Pro klinické využití byla nutná pro zvýšení jejich stability a odstranění některých nežádoucích účinků jejich chemická modifikace, a dále pak vazba na další substance, které umožní jejich cílený transport do požadované tkáně. Celá řada těchto léků je již v pokročilých fázích klinických studií a některé z nich vstupují na farmaceutický trh.
Biological therapy, whose mechanism of action is the use of monoclonal antibodies against a protein, has been used in clinical practice for many years. However, new drugs from the group of biological therapies that act on the principle of RNA interference are now entering clinical practice. RNA interference is the process by which cells in all living organisms regulate the expression of their genes, and in which the transfer of information about the synthesis of a particular protein between DNA and ribosomes can be stopped. For therapeutic purposes, this effect is achieved by administering artificially synthesized oligonucleotides – short chains of RNA with a precise nucleoside sequence. These are either short stretches of double- stranded RNA or single-stranded oligonucleotides. For clinical use, their chemical modification was necessary to increase their stability and remove some of their side effects, and then binding to other substances to allow their targeted transport to the desired tissue. A number of these drugs are already in advanced stages of clinical trials, and some are entering the pharmaceutical market.
Auxin and cytokinin belong to the 'magnificent seven' plant hormones, having tightly interconnected pathways leading to common as well as opposing effects on plant morphogenesis. Tremendous progress in the past years has yielded a broad understanding of their signalling, metabolism, regulatory pathways, transcriptional networks, and signalling cross-talk. One of the rapidly expanding areas of auxin and cytokinin research concerns their RNA regulatory networks. This review summarizes current knowledge about post-transcriptional gene silencing, the role of non-coding RNAs, the regulation of translation, and alternative splicing of auxin- and cytokinin-related genes. In addition, the role of tRNA-bound cytokinins is also discussed. We highlight the most recent publications dealing with this topic and underline the role of RNA processing in auxin- and cytokinin-mediated growth and development.
- MeSH
- alternativní sestřih * MeSH
- cytokininy genetika metabolismus MeSH
- kyseliny indoloctové metabolismus MeSH
- nekódující RNA metabolismus MeSH
- regulace genové exprese u rostlin * MeSH
- regulátory růstu rostlin genetika metabolismus MeSH
- RNA interference * MeSH
- vývoj rostlin MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
