Background: Argonaute2 protein (Ago2) is a key component of RNA-induced gene silencing complex, which is crucial for microRNA-mediated repression of target genes. The function of Ago2 in the mouse oocyte and early embryonic development is less well characterized but it is likely to have an important role in regulating maternally inherited mRNA. We have examined the role of Ago2 by conditional deletion of the gene in developing oocytes.
Results: Ago2 was deleted specifically in the growing oocytes. Although the Ago2-deficient oocytes are able to develop to mature oocytes, they have abnormal spindles and chromosomes that are unable to cluster together properly. This phenotype is very similar to the phenotype of Dicer-deficient oocytes. We examined the microRNA expression profile in the Ago2-deficient oocyte and found that the expression of most microRNAs was reduced by more than 80%. To determine the downstream genes that are regulated by Ago2, we used microarray analysis on Ago2-deficient oocytes and found that 512 genes were upregulated and 1,073 genes were downregulated (FC > 2, P < 0.05).
Conclusion: Our study shows that Ago2 has a key function in the mouse oocyte through global regulation of microRNA stability, and through this mechanism it affects gene expression in developing oocytes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736168 | PMC |
| http://dx.doi.org/10.1186/1756-8935-2-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Infectious myonecrosis virus (IMNV) induces upregulation of RNAi-related genes in white shrimp Penaeus vannamei.
Dev Comp Immunol
January 2025
Laboratório de Biologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal de Rio Grande (FURG), Av. Itália, Km 8, CEP 96203-900, Rio Grande, RS, Brazil.
Article Synopsis
- Infectious myonecrosis virus (IMNV) leads to considerable economic and social challenges in shrimp farming in the U.S. and Asia.
- This study focused on the transcriptional changes of key RNAi mechanism genes (Sid-1, Dicer-2, Argonaute-2) in Penaeus vannamei infected with varying concentrations of IMNV.
- Results showed that higher IMNV concentrations impacted transcription levels of these genes, but the overall viral load remained unchanged, suggesting Sid-1 mRNA expression as a potential marker for monitoring viral replication in shrimp farming.
Design, synthesis, molecular dynamics and gene silencing studies of novel therapeutic HIF-1α siRNAs in hypoxic cancer cells.
Int J Biol Macromol
December 2024
Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow 226 025, Uttar Pradesh, India. Electronic address:
Hypoxia inducible factors (HIFs) are heterodimeric proteins that belong to a small group of transcription factors, which mainly regulates transcription of genes under hypoxic conditions. Particularly, oxygen sensing subunit of HIF-1α is a predominant subtype that heterodimerizes with oxygen-independent HIF-1β subunit, to trigger the transcription of hypoxia responsive genes. Due to poor supply of blood and rapid division of cancerous cells, tumor microenvironment exhibits low oxygen condition and therefore increased levels of HIF-1α.
View Article and Find Full Text PDFTarget cleavage and gene silencing by Argonautes with cityRNAs.
Cell Rep
October 2024
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular and Developmental Biology, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. Electronic address:
TinyRNAs (tyRNAs) are ≤17-nt guide RNAs associated with Argonaute proteins (AGOs), and certain 14-nt cleavage-inducing tyRNAs (cityRNAs) catalytically activate human Argonaute3 (AGO3). We present the crystal structure of AGO3 in complex with a cityRNA, 14-nt miR-20a, and its complementary target, revealing a different trajectory for the guide-target duplex from that of its ∼22-nt microRNA-associated AGO counterpart. cityRNA-loaded Argonaute2 (AGO2) and AGO3 enhance their endonuclease activity when the immediate 5' upstream region of the tyRNA target site (UTy) includes sequences with low affinity for AGO.
View Article and Find Full Text PDFUnderstanding the Role of miR-29a in the Regulation of RAG1, a Gene Associated with the Development of the Immune System.
J Immunol
October 2024
Department of Biochemistry, Indian Institute of Science, Bangalore, India.
The process of Ag receptor diversity is initiated by RAGs consisting of RAG1 and RAG2 in developing lymphocytes. Besides its role as a sequence-specific nuclease during V(D)J recombination, RAGs can also act as a structure-specific nuclease leading to genome instability. Thus, regulation of RAG expression is essential to maintaining genome stability.
View Article and Find Full Text PDFThe structural basis for RNA slicing by human Argonaute2.
bioRxiv
August 2024
Department of Biology, Massachusetts Institute of Technology, 31 Ames Street, Cambridge, MA, 02139, USA.
Argonaute (AGO) proteins associate with guide RNAs to form complexes that slice transcripts that pair to the guide. This slicing drives post-transcriptional gene-silencing pathways that are essential for many eukaryotes and the basis for new clinical therapies. Despite this importance, structural information on eukaryotic AGOs in a fully paired, slicing-competent conformation-hypothesized to be intrinsically unstable-has been lacking.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!