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The RNA–RNA base pairing potential of human Dicer and Ago2 proteins
- Source :
- Cellular and Molecular Life Sciences
- Publication Year :
- 2019
- Publisher :
- Springer International Publishing, 2019.
-
Abstract
- The ribonuclease Dicer produces microRNAs (miRNAs) and small interfering RNAs that are handed over to Ago proteins to control gene expression by targeting complementary sequences within transcripts. Interestingly, a growing number of reports have demonstrated that the activity of Dicer may extend beyond the biogenesis of small regulatory RNAs. Among them, a report from our latest studies revealed that human Dicer facilitates base pairing of complementary sequences present in two nucleic acids, thus acting as a nucleic acid annealer. Accordingly, in this manuscript, we address how RNA structure influences the annealing activity of human Dicer. We show that Dicer supports hybridization between a small RNA and a complementary sequence of a longer RNA in vitro, even when both complementary sequences are trapped within secondary structures. Moreover, we show that under applied conditions, human Ago2, a core component of RNA-induced silencing complex, displays very limited annealing activity. Based on the available data from new-generation sequencing experiments regarding the RNA pool bound to Dicer in vivo, we show that multiple Dicer-binding sites within mRNAs also contain miRNA targets. Subsequently, we demonstrate in vitro that Dicer but not Ago2 can anneal miRNA to its target present within mRNA. We hypothesize that not all miRNA duplexes are handed over to Ago proteins. Instead, miRNA-Dicer complexes could target specific sequences within transcripts and either compete or cooperate for binding sites with miRNA-Ago complexes. Thus, not only Ago but also Dicer might be directly involved in the posttranscriptional control of gene expression. Electronic supplementary material The online version of this article (10.1007/s00018-019-03344-6) contains supplementary material, which is available to authorized users.
- Subjects :
- Ribonuclease III
Small RNA
genetic processes
RNA-annealing activity
RNA-binding proteins
DEAD-box RNA Helicases
03 medical and health sciences
Cellular and Molecular Neuroscience
mRNA fate
microRNA
Gene expression
Annealing activity
Gene silencing
Humans
RNA-Induced Silencing Complex
Nucleic acid structure
Molecular Biology
Base Pairing
Translational regulator
030304 developmental biology
Pharmacology
0303 health sciences
biology
Chemistry
RNA annealers
030302 biochemistry & molecular biology
fungi
RNA
food and beverages
Cell Biology
Cell biology
enzymes and coenzymes (carbohydrates)
Gene Expression Regulation
miRNA/siRNA pathways
Argonaute Proteins
biology.protein
Molecular Medicine
Original Article
Dicer
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 14209071 and 1420682X
- Volume :
- 77
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Life Sciences
- Accession number :
- edsair.doi.dedup.....1150f82199e9a2c888b671094fe7e286