H2020Индивидуална стипендия2020–2022

uTSSreg · Regulation of mammalian genes by new classes of promoter proximal transcription start sites

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

Период: 2020-04-01 → 2022-03-31
Финансиране от ЕС: 219 312 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Нестабилните места за начало на транскрипцията в гените на бозайниците създават краткотрайни молекули, които бързо се разграждат. Разбирането на тези процеси помага за откриването на нови механизми за регулиране на генната активност, което е важно за медицината и биологията.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Regulation of mammalian genes by new classes of promoter proximal transcription start sites

The development of high-throughput sequencing methods has revealed that mammalian genomes have complex transcription patterns that generate far more spurious transcripts than RNA molecules from conventional protein-coding genes. However, the extent and content of the information encoded by such extensive transcription and the functions that the generated noncoding RNA can perform remain to be understood. RNA exosomes are evolutionarily conserved multisubunit complexes of 9 core subunits, including RRP40, with 3 '-5' exo- and endo- nucleolytic activities and in many cases, have been shown to eliminate spurious transcripts from the nucleus rapidly. Interestingly, unpublished data recently from my lab shows that there are multiple transcription start sites (TSSs) in the promoter region, many of which produce exosome-sensitive products in hundreds of cases. Therefore, there may be previously unknown transcriptional events associated with promoters that affect the regulation of gene activity. Collecting these examples and studying the mechanisms makes it possible to discover entirely new principles of gene regulation and elucidate the molecular mechanisms underlying them. Understanding these new mechanisms is also of great importance in the related fields of developmental biology and medicine. The overarching aim of the proposed project is to locate spurious transcription events and to investigate the impact of selected cases on local gene expression. Employing rapid depletion of nuclear RNA decay activities, I will construct a comprehensive map of transcription events, which are normally 'hidden' by RNA turnover, therefore producing unstable TSSs (uTSSs).

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

Цел на проекта

Regulation and fidelity of gene expression is fundamental to the differentiation and maintenance of living organisms. Moreover, understanding how genes are regulated is an essential research question of importance for biomedical application. Although our knowledge about key factors influencing gene expression has increased substantially over the past years, the complexity of gene expression regulation remains elusive. In this project, I intend to discover novel gene expression regulatory circuits operating in mammalian genomes facilitated by pervasive transcription. Although some scattered examples of how pervasive transcription may regulate gene promoter activity exist, no systematic study has been conducted. Here, I will address this question by using a new protein depletion strategy, developed in the host laboratory, to inactivate the nuclear exosome, a major 3’-to-5’ ribonuclease complex, and its co-factors in HeLa and mouse embryonic stem (mES) cells, thus, to create an ideal situation to observe ‘hidden’ cellular transcription events, which would not normally be visible. I intend to assess whether and how this ‘hidden’ transcription contributes to the regulation of promoter activity in HeLa and mES cells, further expanding our knowledge of the regulation of protein-coding genes and ultimately revealing the extent of regulation instigated by pervasive transcription. This study will lay a foundation for future research in the field and at the same time provide novel conceptual information, which might be exploited in prevention or treatment of human diseases.

Оригинален текст от CORDIS (на английски).

Участници

AARHUS UNIVERSITET · Aarhus CКоординаторДания