3W-RGB · Identification of whether, in which aspects and by which function, a RNA binding protein, KH-type splicing regulatory protein governs development and function of B cell, a type of white blood cell""
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2013-07-01 → 2015-06-30
- Финансиране от ЕС
- 299 558 €
- Участници
- 1
- Схема
- MC-IIF
Линиите свързват координатора с партньорите.
Накратко на български
B-клетките и ролята на молекулата miR-155 се анализират, за да се разбере как тя предпазва определени бели кръвни клетки от унищожение. Това помага да се разбере как организмът създава ефективни антитела срещу патогени и как се развиват някои тумори.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Identification of whether, in which aspects and by which function, a RNA binding protein, KH-type splicing regulatory protein governs development and function of B cell, a type of white blood cell
The production of high-affinity antibodies by B cells is essential for the clearance of pathogens. Increased antibody affinity for antigen is achieved by the process of affinity maturation in germinal centres (GCs). This is an iterative process in which B cells re-cycle between proliferation and the acquisition of mutations and antigen-based positive selection of the highest-affinity B cell clones. The post-transcriptional regulator microRNA (miR)-155 is critical for efficient affinity maturation and the maintenance of the GCs. We first focused on the function of the miR processing protein KSRP in the regulation of B cell function via its effect on miR-155. However we concluded that KSRP does not play a major role in GC-B cells based on experiments using KSRP-deficient mice and therefore shifted the miR-155 itself rather than the miR-155 processing protein. In order to understand the cellular and molecular mechanism by which miR-155 regulates GC responses, we utilised a miR-155 reporter mouse strain and showed that miR-155 is co-expressed with the proto-oncogene c-Myc in positively-selected B cells. Functionally, miR-155 protects c-Myc+ positively-selected B cells from apoptosis allowing their clonal expansion, which explains why deletion of miR-155 results in impaired affinity maturation and the premature collapse of GCs. Molecularly, miR-155 directly inhibits the Jumonji family member Jarid2, which we identify here as a novel component in the GC response, to promote GC-B cell survival. Our findings also suggest a basis for cooperation between c-Myc and miR-155 during the normal GC response, which may explain a longstanding enigma of how c-Myc and miR-155 can collaboratively function as oncogenes.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The immune system is a biological defence against diseases including virus and bacterial infections. A type of white blood cell, B cell, is causative for production of antibodies, key effectors to identify and neutralize viruses or bacteria. B cell can produce high affinity antibodies rapidly upon re-exposure to the same infectious agent, making B cell a key player for immunological memory, a principle of vaccination. Thus, full understanding on B cell biology is crucial for improvement of vaccination as well as prevention of B cell-diseases including B cell-cancers, immunodeficiency, a malfunction of immune system, and autoimmunity caused by aberrant immune response against its own cells and tissues. Recent discovery of microRNAs (miR)s, short RNAs promoting mRNA decay, has highlighted the importance of the regulation of mRNA decay in B cell development and function. Especially, miR-155 has been identified as an essential regulator for antibody production and its biogenesis appears to be mediated by a RNA-binding protein (RBP), KH-type splicing regulatory protein (KSRP). KSRP is a versatile protein with abilities to facilitate miR generation, mRNA decay and splicing, a modification process of newly generated pre-mRNA, and it has been suggested that KSRP controls several key genes related to B cell functions. Thus, we propose that KSRP is an important gene regulator of B cell biology. The aim of this proposal is to identify Whether, in Which aspects and by Which function, the RBP, KSRP, Governs B cell development and function in B cell-intrinsic manner. To achieve this aim, we will perform phenotypic analysis using a unique mouse model system lacking KSRP gene expression. Bioinformatic analysis will allow identifying the genes that KSRP regulates in the context of observed phenotype. The results can generate new insights for gene regulation mechanisms in B cell biology and aid to pave a way for improvement of vaccination and novel treatments for B cell-diseases.""
Оригинален текст от CORDIS (на английски).
Участници
- THE BABRAHAM INSTITUTE · CambridgeКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз