Pathologic effects of RNase-L dysregulation in immunity and proliferative control.
Pathologic effects of RNase-L dysregulation in immunity and proliferative control.
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DOI：
10.2741/s298
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Hassel BA
中科院分区：
文献类型：
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作者：
Ezelle HJ;Hassel BA
核糖核酸内切酶RNase-L是介导抗病毒、抗增殖和免疫调节活性的RNA切割途径的末端组分。RNase-L的失活或失调与免疫应答受损和癌症风险增加相关，因此其活性受到严格控制，并且需要变构激活剂，2 '，5'-连接的寡腺苷酸，用于酶活性。RNase-L的生物活性是RNA切割的直接和间接作用的结果，并且微阵列分析已经揭示RNase-L在多个水平上影响基因表达程序。RNase-L调节的RNA的鉴定提供了对其发挥抗增殖、促凋亡、衰老诱导和先天免疫活性的潜在机制的深入了解。RNase-L蛋白相互作用物已被鉴定为具有调节功能，并被认为是其生物学功能的替代机制。因此，虽然仅了解RNase-L活性子集的分子细节，但其通过小分子的调节以及在宿主防御中的关键作用和作为候选肿瘤抑制因子使其成为有希望的治疗靶点。
The endoribonuclease RNase-L is the terminal component of an RNA cleavage pathway that mediates antiviral, antiproliferative and immunomodulatory activities. Inactivation or dysregulation of RNase-L is associated with a compromised immune response and increased risk of cancer, accordingly its activity is tightly controlled and requires an allosteric activator, 2',5'-linked oligoadenylates, for enzymatic activity. The biological activities of RNase-L are a result of direct and indirect effects of RNA cleavage and microarray analyses have revealed that RNase-L impacts the gene expression program at multiple levels. The identification of RNase-L-regulated RNAs has provided insights into potential mechanisms by which it exerts antiproliferative, proapoptotic, senescence-inducing and innate immune activities. RNase-L protein interactors have been identified that serve regulatory functions and are implicated as alternate mechanisms of its biologic functions. Thus while the molecular details are understood for only a subset of RNase-L activities, its regulation by small molecules and critical roles in host defense and as a candidate tumor suppressor make it a promising therapeutic target.