A Dynamic Search Process Underlies MicroRNA Targeting
نویسندگان
چکیده
Argonaute proteins play a central role in mediating post-transcriptional gene regulation by microRNAs (miRNAs). Argonautes use the nucleotide sequences in miRNAs as guides for identifying target messenger RNAs for repression. Here, we used single-molecule FRET to directly visualize how human Argonaute-2 (Ago2) searches for and identifies target sites in RNAs complementary to its miRNA guide. Our results suggest that Ago2 initially scans for target sites with complementarity to nucleotides 2-4 of the miRNA. This initial transient interaction propagates into a stable association when target complementarity extends to nucleotides 2-8. This stepwise recognition process is coupled to lateral diffusion of Ago2 along the target RNA, which promotes the target search by enhancing the retention of Ago2 on the RNA. The combined results reveal the mechanisms that Argonaute likely uses to efficiently identify miRNA target sites within the vast and dynamic agglomeration of RNA molecules in the living cell.
منابع مشابه
MicroRNA targeting of CoREST controls polarization of migrating cortical neurons.
The migration of cortical projection neurons is a multistep process characterized by dynamic cell shape remodeling. The molecular basis of these changes remains elusive, and the present work describes how microRNAs (miRNAs) control neuronal polarization during radial migration. We show that miR-22 and miR-124 are expressed in the cortical wall where they target components of the CoREST/REST tra...
متن کاملCancer virotherapy: Targeting cancer cells by microRNA mechanism for selective replication of oncolytic viruses in these cells
Cancer, as one of the most serious public health problems, is the second-leading cause of death in the world after cardiovascular disease. The number of patients and the resulting mortality are increasing worldwide; therefore, early diagnosis, prevention, and effective treatment of cancer are very important. Current treatments such as chemotherapy and radiation therapy are often non-selective a...
متن کاملmicroRNA-29a functions as a tumor suppressor in nasopharyngeal carcinoma 5-8F cells through targeting VEGF
Objective(s): microRNA-29 (miR-29) family miRNAs have been mentioned as tumor suppressive genes in several human cancers. The purpose of this study was to investigate the function of miR-29a in nasopharyngeal carcinoma (NPC) cells. Materials and Methods: Human NPC cell line 5-8F was transfected with mimic, inhibitor or scrambled controls...
متن کاملMicroRNA-205 inhibits renal cells apoptosis via targeting CMTM4
Objective(s):MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles in kidney development, homeostasis and disease, and participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). In the present study, we elucidated the role of microR...
متن کاملMicroRNA-7 activates Nrf2 pathway by targeting Keap1 expression.
Nuclear factor E2-related factor 2 (Nrf2) is a key transcription factor that regulates the expression of a number of antioxidant and detoxifying genes that provide cellular protection against various stressors including reactive oxygen species (ROS). Nrf2 activity is tightly regulated by a cytoplasmic inhibitory protein called Kelch-like ECH-associated protein 1 (Keap1). The mechanism that cont...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cell
دوره 162 شماره
صفحات -
تاریخ انتشار 2015