Abstract
In animals, the double-stranded RNA-specific endonuclease Dicer produces two classes of functionally distinct, tiny RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). miRNAs regulate mRNA translation, whereas siRNAs direct RNA destruction via the RNA interference (RNAi) pathway. Here we show that, in human cell extracts, the miRNA let-7 naturally enters the RNAi pathway, which suggests that only the degree of complementarity between a miRNA and its RNA target determines its function. Human let-7 is a component of a previously identified, miRNA-containing ribonucleoprotein particle, which we show is an RNAi enzyme complex. Each let-7-containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells.
MeSH Terms
Adenosine Triphosphate/metabolism
Animals
Argonaute Proteins
Base Pairing
Base Sequence
Cell Extracts
Cytoplasm/metabolism
DEAD Box Protein 20
DEAD-box RNA Helicases
Drosophila melanogaster/genetics
Endoribonucleases/metabolism
Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
Gene Silencing
HeLa Cells
Humans
MicroRNAs
Minor Histocompatibility Antigens
Models, Genetic
Nuclear Proteins/metabolism
Peptide Initiation Factors/metabolism
Protein Biosynthesis
RNA Helicases/metabolism
RNA, Antisense/chemistry,metabolism
RNA, Double-Stranded/chemistry,metabolism
RNA, Messenger/chemistry,metabolism
RNA, Small Interfering
RNA, Untranslated/chemistry,metabolism
RNA-Induced Silencing Complex
Ribonuclease III
Ribonucleoproteins/metabolism
Ribonucleoproteins, Small Nuclear
Chemicals
AGO1 protein, human
AGO2 protein, human
Argonaute Proteins
Cell Extracts
Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
GEMIN4 protein, human
MicroRNAs
Minor Histocompatibility Antigens
Nuclear Proteins
Peptide Initiation Factors
RNA, Antisense
RNA, Double-Stranded
RNA, Messenger
RNA, Small Interfering
RNA, Untranslated
RNA-Induced Silencing Complex
Ribonucleoproteins
Ribonucleoproteins, Small Nuclear
Adenosine Triphosphate
Endoribonucleases
Ribonuclease III
DDX20 protein, human
DEAD Box Protein 20
DEAD-box RNA Helicases
RNA Helicases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hutvágner György
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA.
Zamore Phillip D