Eylem Seç
Role of the RNA Modification N6-methyladenosine in Normal Hematopoiesis & Disease
Başlık:
Role of the RNA Modification N6-methyladenosine in Normal Hematopoiesis & Disease
Yazar:
Vasic, Radovan, author.
ISBN:
9780438132436
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (98 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Stephanie Halene Committee members: Jun Lu; Manoj Pillai.
Özet:
N6-methyladenosine (m6A) is the most abundant modified nucleotide occurring in mRNA, with key roles in RNA metabolism and regulation of gene expression. Proposed effects of m6A modification of RNA transcripts include effects on transcript half-life, translation efficiency, splicing and miRNA biogenesis. Importantly, m6A is the only known dynamic RNA modification, with deposition mediated by the "writer" METTL3, and demethylation carried out by the "erasers" ALKBH5 and FTO. We hypothesized a role for m6A in hematopoiesis, with potential disease relevance in myeloid malignancies.
To gain an understanding of the effects of m6A on normal hematopoiesis and myeloid malignancies such as the myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), we developed conditional knockout mice for the m 6A writer METTL3, and the eraser ALKBH5. We find that deletion of METTL3 results in embryonic lethality, with an accumulation of dysfunctional hematopoietic stem cells (HSCs) that are incompetent in hematopoietic rescue assays. We further characterize disturbances in myeloid & lymphoid lineage differentiation. Deletion of ALKBH5 does not result in steady-state hematopoietic dysfunction, but results in hematopoietic stem cell deficiencies in competitive transplant assays.
We propose that deletion of METTL3 locks HSCs in a naive multipotent state, and hypothesize that ALKBH5 exerts effects on HSC function that are yet to be characterized.
Notlar:
School code: 0265
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(688778.1) | 688778-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.