title: Enhanced translation by Nucleolin via G-rich elements in coding and non-coding regions of target mRNAs.
abstract: RNA-binding proteins (RBPs) regulate gene expression at many post-transcriptional levels, including mRNA stability and translation. The RBP nucleolin, with four RNA-recognition motifs, has been implicated in cell proliferation, carcinogenesis and viral infection. However, the subset of nucleolin target mRNAs and the influence of nucleolin on their expression had not been studied at a transcriptome-wide level. Here, we globally identified nucleolin target transcripts, many of which encoded cell growth- and cancer-related proteins, and used them to find a signature motif on nucleolin target mRNAs. Surprisingly, this motif was very rich in G residues and was not only found in the 3'-untranslated region (UTR), but also in the coding region (CR) and 5'-UTR. Nucleolin enhanced the translation of mRNAs bearing the G-rich motif, since silencing nucleolin did not change target mRNA stability, but decreased the size of polysomes forming on target transcripts and lowered the abundance of the encoded proteins. In summary, nucleolin binds G-rich sequences in the CR and UTRs of target mRNAs, many of which encode cancer proteins, and enhances their translation.
authors: Laboratory of Molecular Biology and Immunology, National Institute on Aging - Intramural Research Program, NIH, Baltimore, MD 21224, USA. abdelmohsenk@grc.nia.nih.gov
authors: Kotb
authors: K
authors: Abdelmohsen
authors: Kumiko
authors: K
authors: Tominaga
authors: Eun Kyung
authors: EK
authors: Lee
authors: Subramanya
authors: S
authors: Srikantan
authors: Min-Ju
authors: MJ
authors: Kang
authors: Mihee M
authors: MM
authors: Kim
authors: Roza
authors: R
authors: Selimyan
authors: Jennifer L
authors: JL
authors: Martindale
authors: Xiaoling
authors: X
authors: Yang
authors: France
authors: F
authors: Carrier
authors: Ming
authors: M
authors: Zhan
authors: Kevin G
authors: KG
authors: Becker
authors: Myriam
authors: M
authors: Gorospe
mesh_terms: D017930:Genes, Reporter; D006147:Guanine / Q000032:analysis; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D059372:Nucleotide Motifs; D010750:Phosphoproteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D059467:Transcriptome; D020506:Untranslated Regions; D000097796:Nucleolin
chemical_list: D006147:Guanine; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020506:Untranslated Regions; D000097796:Nucleolin