title: The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame.
abstract: The first round of translation occurs on mRNAs bound by nuclear cap-binding complex (CBC), which is composed of nuclear cap-binding protein 80 and 20 (CBP80/20). During this round of translation, aberrant mRNAs are recognized and downregulated in abundance by nonsense-mediated mRNA decay (NMD), which is one of the mRNA quality control mechanisms. Here, our microarray analysis reveals that the level of cyclin-dependent kinase inhibitor 1A (CDKN1A; also known as Waf1/p21) mRNAs increases in cells depleted of cellular NMD factors. Intriguingly, CDKN1A mRNA contains an upstream open reading frame (uORF), which is a NMD-inducing feature. Using chimeric reporter constructs, we find that the uORF of CDKN1A mRNA negatively modulates translation of the main downstream ORF. These findings provide biological insights into the possible role of NMD in diverse biological pathways mediated by CDKN1A.
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors: Kyoung Mi
authors: KM
authors: Kim
authors: Hana
authors: H
authors: Cho
authors: Yoon Ki
authors: YK
authors: Kim
mesh_terms: D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis / Q000235:genetics*; D020365:RNA Helicases; D020871:RNA Stability; D012333:RNA, Messenger / Q000096:biosynthesis / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C437718:PNRC2 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human