H2020Индивидуална стипендия2015–2017

Human Rpc5 · RNA Polymerase III Rpc4/Rpc5 subcomplex and Selenocysteine tRNA transcription

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-05-01 → 2017-04-30
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Взаимодействието между протеина Rpc5 (част от ензима РНК полимераза III) и фактора Brf2 се изучава при процеса на преписване на ДНК в РНК. Разбирането на този механизъм помага за изясняване на причините за развитието на различни видове рак.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

RNA Polymerase III Rpc4/Rpc5 subcomplex and Selenocysteine tRNA transcription

To a great extent, the development of human diseases such as cancer are caused by the modification of some function performed by our cells. If the cells cannot correctly execute that function (or they execute it in excess), the whole body is affected and, in the end, the disease progresses. The execution of these function is mediated by molecular machines (or enzymes) present inside our cells. One of these machines, known as RNA Polymerase III, participates in a process known as transcription, which is the conversion of our DNA genes into a “readable” molecule known as RNA. This is an essential function that takes part in all the cells of our body and its alteration causes catastrophic consequences. In order to correctly perform this function, the enzyme needs to be bound to the DNA and it requires the participation of other factors known as Transcription Factors. To understand how the disease appears and progresses we first need to understand how the basic cellular machines work. In the case of the RNA polymerase III, we still don’t know how it gets bound to the DNA and, given its direct relevance in cancer development, understanding this process might have a profound impact in biomedical research. The overall objective of the project is to study the hypothetical interaction between a part of the RNA Polymerase III known as Rpc5 and a transcription factor known as Brf2, whose levels are altered in several cancers.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

In higher eukaryotes, the RNA polymerase III (Pol III) participates in the transcription of small RNAs such as the tRNAs. RNA polymerase recruitment to their specific promoter relies on the activity of several transcription factors. Brf2 is a transcription factor that exclusively recruits RNA Pol III at the selenocysteine tRNA (tRNASec). Unpublished work from our group has unravelled an unanticipated central role of Brf2 in the oxidative stress response pathway, by acting as a cellular blockade during prolonged oxidative stress.We are interested in understanding the molecular determinants that govern RNA Pol III recruitment at tRNASec promoter and its interaction with Brf2-bound promoters. In general, RNA Pol III subunit’s size is conserved amongst the eukaryotic kingdom. However, an exception is the human Rpc5 subunit, whose C terminus has 450 residues that are not present in its yeast counterpart C37. Similarly to Brf2, the Rpc5 C-terminal extension is only present in higher metazoans, which suggests a phylogenetic link between these two proteins. The recruiting mechanism of RNA Pol III to Brf2-dependent promoters has not been described to date. Preliminary results in our lab provide evidences that indeed Rpc5 C terminus is responsible for the accurate recruitment of RNA Pol III at TBP/Brf2/DNA complex. Interestingly, structural homology predictions indicated that the human Rpc5 C-terminal extension is a eukaryotic homologue of the prokaryotic protein SelB, a factor that interacts with the tRNASec and with a specific region of mRNAs, the SECIS-element, during translation of SeCys containing proteins. This similarity suggests a regulatory role for Rpc5 C terminus in the interaction with the SECIS-element and/or the tRNASec.Our main objectives are to determine the structure of the Rpc5 C terminus in isolation and in complex with Brf2/TBP/DNA by X-ray crystallography and to characterise the role of Rpc5 C terminus in the context of tRNASec transcription.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUTE OF CANCER RESEARCH: THE ROYAL CANCER HOSPITAL LBG · LondonКоординаторОбединеното кралство