Regulation of erythropoiesis by the miR-144/451 microRNA locus

miR-144/451 microRNA 位点对红细胞生成的调节

基本信息

  • 批准号:
    8730772
  • 负责人:
  • 金额:
    $ 6.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-30 至 2014-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): We seek to discover new, medically relevant mechanisms governing red blood cell formation (erythropoiesis). Recently identified small non-coding RNAs, termed microRNAs (miRs), profoundly influence normal development and stress responses in virtually all tissues. MiRs suppress protein synthesis by inhibiting the translation and stability of specific target mRNAs that are recognized via Watson-Crick base pairing. This proposal investigates the role of miRs 144 and 451, which are encoded on a single gene locus that is strongly induced during erythropoiesis. In zebrafish and mice, loss of miR-451 impairs erythropoiesis, sensitizes mature erythrocytes to destruction by oxidant stress and induces erythroid precursor apoptosis after acute anemia. Preliminary data indicate that miR-144/451 regulates iron uptake, survival, maturation, and mitochondrial energy metabolism during erythropoiesis through confirmed target mRNAs including Rab14, Myc, Ywhaz, and Cab39. We will investigate further the mechanisms through which miRs 144 and 451 control erythropoiesis at baseline, and during disease-related stresses including blood loss, iron deficiency, and unbalanced hemoglobin production (thalassemia). Our work should provide new insights into erythroid development and associated disorders including myeloproliferative syndromes and various anemias. Moreover, knowledge gained through our studies of erythropoiesis should be applicable to other biological processes where miR-451 is believed to function, including protection against myocardial stress, regulation of immune responses and as a tumor suppressor in numerous malignancies.
描述(由申请人提供):我们寻求发现新的,医学相关的机制,控制红细胞形成(红细胞生成)。最近发现的小的非编码RNA,称为microRNA(miRs),深刻影响几乎所有组织的正常发育和应激反应。miR通过抑制经由沃森-克里克碱基配对识别的特定靶mRNA的翻译和稳定性来抑制蛋白质合成。该提案研究了miR 144和451的作用,miR 144和451在红细胞生成期间强烈诱导的单个基因位点上编码。在斑马鱼和小鼠中,miR-451的缺失损害红细胞生成,使成熟红细胞对氧化应激的破坏敏感,并诱导急性贫血后的红细胞前体细胞凋亡。初步数据表明,miR-144/451通过确定的靶mRNA(包括Rab 14、Myc、Ywhaz和Cab 39)调节红细胞生成过程中的铁摄取、存活、成熟和线粒体能量代谢。我们将进一步研究miRs 144和451在基线时以及在疾病相关应激(包括失血、缺铁和血红蛋白产生不平衡(地中海贫血))期间控制红细胞生成的机制。我们的工作应该提供新的见解红细胞发育和相关疾病,包括骨髓增生综合征和各种贫血。此外,通过我们对红细胞生成的研究获得的知识应该适用于miR-451被认为发挥作用的其他生物过程,包括保护心肌应激、调节免疫反应以及作为许多恶性肿瘤的肿瘤抑制因子。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Mitchell J Weiss其他文献

Adenine Base Editing Improves Erythropoiesis in Diamond-Blackfan Anemia Syndrome Patient-Derived Induced Pluripotent Stem Cells
  • DOI:
    10.1182/blood-2024-209312
  • 发表时间:
    2024-11-05
  • 期刊:
  • 影响因子:
  • 作者:
    Shruthi Suryaprakash;Lei Han;Garret Manquen;Varun Katta;Damian Krzyzanowski;Jayaram Prasad;Nikitha Nimmagada;Kalin Mayberry;Nana Liu;Yan Ju;Yu Yao;Kelsey Ray;Marcin Wlodarski;Shengdar Q Tsai;Jonathan S Yen;Mitchell J Weiss;Senthil Velan Bhoopalan
  • 通讯作者:
    Senthil Velan Bhoopalan
Testing Rapamycin As an Anti-Adhesion Therapy for Sickle Cell Disease
  • DOI:
    10.1182/blood-2024-212384
  • 发表时间:
    2024-11-05
  • 期刊:
  • 影响因子:
  • 作者:
    Danitza Nebor;Mitchell J Weiss;Jonathan M. Flanagan
  • 通讯作者:
    Jonathan M. Flanagan
Hematopoietic Stem Cells Supporting Fetal Erythropoiesis Are Differentially Regulated By Small and Large Ribosomal Subunits
  • DOI:
    10.1182/blood-2024-210699
  • 发表时间:
    2024-11-05
  • 期刊:
  • 影响因子:
  • 作者:
    Yuefeng Tang;Te Ling;Rashid Mehmood;Mushran Khan;Julien Papoin;James Palis;Laurie A. Steiner;Sébastien Durand;Leonard I. Zon;Senthil Velan Bhoopalan;Mitchell J Weiss;Jeffrey Michael Lipton;Naomi Taylor;Patrick G. Gallagher;Mohandas Narla;John D. Crispino;Lionel Blanc
  • 通讯作者:
    Lionel Blanc
Identification of Breakpoints of emRHD/em Hybrid Alleles By Long-Read Sequencing
通过长读长测序鉴定 emRHD/em 杂合等位基因的断点
  • DOI:
    10.1182/blood-2024-198223
  • 发表时间:
    2024-11-05
  • 期刊:
  • 影响因子:
    23.100
  • 作者:
    Ti-Cheng Chang;Jing Yu;Bensheng Ju;Melanie Loyd;Granger Ridout;Geoffrey A.M. Neale;Jane S Hankins;Mitchell J Weiss;Gorka Ochoa;Sunitha Vege;Stella T. Chou;John Easton;Yan Zheng
  • 通讯作者:
    Yan Zheng
Motixafortide for Hematopoietic Stem and Progenitor Cell Mobilization and Collection in Sickle Cell Disease
  • DOI:
    10.1182/blood-2024-200330
  • 发表时间:
    2024-11-05
  • 期刊:
  • 影响因子:
  • 作者:
    Alexis Kristine Leonard;Akshay Sharma;Yogindra Persaud;Parul Rai;Darla Pickett;Renee Massey;Neha Das Gupta;Subodh Selukar;Salem M. Akel;Leigh Poston;Yan Zheng;Ella Sorani;Irit Gliko Kabir;Mitchell J Weiss;Stephen Gottschalk;Julie Kanter;Matthew Hsieh;John Tisdale
  • 通讯作者:
    John Tisdale

Mitchell J Weiss的其他文献

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{{ truncateString('Mitchell J Weiss', 18)}}的其他基金

ULK-mediated autophagy of α-globin in ß-thalassemia
α-地中海贫血中 ULK 介导的 α-珠蛋白自噬
  • 批准号:
    10649565
  • 财政年份:
    2022
  • 资助金额:
    $ 6.27万
  • 项目类别:
ULK-mediated autophagy of α-globin in ß-thalassemia
α-地中海贫血中 ULK 介导的 α-珠蛋白自噬
  • 批准号:
    10539754
  • 财政年份:
    2022
  • 资助金额:
    $ 6.27万
  • 项目类别:
Core B: Human Stem Cell Core
核心B:人类干细胞核心
  • 批准号:
    8698736
  • 财政年份:
    2014
  • 资助金额:
    $ 6.27万
  • 项目类别:
Trim58 and the Ubiquitin Proteasome System in Erythro-megakaryopoiesis
Trim58 和红细胞巨核细胞生成中的泛素蛋白酶体系统
  • 批准号:
    9242002
  • 财政年份:
    2014
  • 资助金额:
    $ 6.27万
  • 项目类别:
Regulation of erythropoiesis by the miR-144/451 microRNA locus
miR-144/451 microRNA 位点对红细胞生成的调节
  • 批准号:
    8726379
  • 财政年份:
    2014
  • 资助金额:
    $ 6.27万
  • 项目类别:
Trim58 and the Ubiquitin Proteasome System in Erythro-megakaryopoiesis
Trim58 和红细胞巨核细胞生成中的泛素蛋白酶体系统
  • 批准号:
    9025774
  • 财政年份:
    2014
  • 资助金额:
    $ 6.27万
  • 项目类别:
Trim58 and the Ubiquitin Proteasome System in Erythro-megakaryopoiesis
Trim58 和红细胞巨核细胞生成中的泛素蛋白酶体系统
  • 批准号:
    8843634
  • 财政年份:
    2014
  • 资助金额:
    $ 6.27万
  • 项目类别:
Regulation of erythropoiesis by the miR-144/451 microRNA locus
miR-144/451 microRNA 位点对红细胞生成的调节
  • 批准号:
    8868445
  • 财政年份:
    2014
  • 资助金额:
    $ 6.27万
  • 项目类别:
Trim58 and the Ubiquitin Proteasome System in Erythro-megakaryopoiesis
Trim58 和红细胞巨核细胞生成中的泛素蛋白酶体系统
  • 批准号:
    8819535
  • 财政年份:
    2014
  • 资助金额:
    $ 6.27万
  • 项目类别:
Regulation of erythropoiesis by the miR-144/451 microRNA locus
miR-144/451 microRNA 位点对红细胞生成的调节
  • 批准号:
    8546340
  • 财政年份:
    2012
  • 资助金额:
    $ 6.27万
  • 项目类别:

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