Interplay between microRNAs and RNA-binding proteins determines developmental processes.
MicroRNAs (miRNAs) are genes involved in normal development and cancer. They inhibit gene expression by associating with 3'-Untranslated regions (3'UTRs) of messenger RNAs (mRNAs), and are thought to regulate a large proportion of protein coding genes. However, it is becoming apparent that miRNA activity is not necessarily always determined by its expression in the cell. MiRNA activity can be affected by RNA-binding proteins (RBPs). For example, the RNA-binding protein HuR associates with the 3'UTR of the CAT1 mRNA after stress, counteracting the effect of miR-122. Second, we found that the expression of an RNA-binding protein called Dead end (Dnd1) prohibits the function of several miRNAs by blocking the accessibility of target mRNAs.(2) Dnd1 function is essential for proper development of primordial germ cells (PGCs) in zebrafish and mammals, indicating a crucial role for RBP/miRNA interplay on 3'UTRs of mRNAs in developmental decisions. In this perspective we discuss the interplay between RBPs and miRNAs in the context of germ cells and review current observations implicating RBPs in miRNA function.
Kedde
Martijn
M
The Netherlands Cancer Institute, Division of Tumor Biology, Amsterdam, The Netherlands.
Agami
Reuven
R
D000954:Antigens, Surface / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005854:Germ Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism
D000954:Antigens, Surface; D015220:Calcium Channels; C528453:Dnd1 protein, human; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human