New Isoforms of VEGF Are Translated from Alternative Initiation CUG Codons Located in Its 5′UTR

Meiron, Moran; Anunu, Rachel; Scheinman, Eyal J.; Hashmueli, Sharon; Levi, Ben‐Zion

doi:10.1006/bbrc.2001.4684

Cited by 56 publications

(42 citation statements)

References 25 publications

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“…CUG initiation has been reported in few well-documented cases, such as FGF2, VEGF, MYC, and MHC class I transcripts (Hann et al 1988;Vagner et al 1996;Meiron et al 2001;Schwab et al 2003). Additionally, recent studies mapping genome-wide translation initiation sites have suggested that upstream translation initiates frequently from non-AUG codon, most prominently at CUG sites (Ingolia et al 2011;Leek et al 2012).…”

Section: Genetic Determinants Of Variability In Ribosome Occupancymentioning

confidence: 99%

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

et al. 2015

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Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy-many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation.

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Section: Genetic Determinants Of Variability In Ribosome Occupancymentioning

confidence: 99%

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

et al. 2015

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“…In this expression system, translation of the human prepro-NPW polypeptide initiated from a non-AUG start codon, and signal peptide cleavage subsequently occurred at an expected site, but proteolytic processing of the propeptide failed to create the expected C terminus of mature NPW, probably due to an incomplete set of processing enzymes in the COS-7 cells (24) or susceptibility to proteolysis of the C terminus of mature NPW in the culture medium. Natural non-AUG start codons are very rare in eukaryotes, but have been found in c-Myc, fibroblast growth factor-2, and vascular epidermal growth factor (25)(26)(27). In almost all cases, alternate initiation takes place at upstream non-AUG codons in addition to the first in-frame AUG codons.…”

Section: Fig 4 Expression and Purification Of Human Npwmentioning

confidence: 99%

Identification of Neuropeptide W as the Endogenous Ligand for Orphan G-protein-coupled Receptors GPR7 and GPR8

Shimomura

Harada

Goto

et al. 2002

Journal of Biological Chemistry

172

157

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The structurally related orphan G-protein-coupled receptors GPR7 and GPR8 are expressed in the central nervous system, and their ligands have not been identified. Here, we report the identification of the endogenous ligand for both of these receptors. We purified the peptide ligand from porcine hypothalamus using stable Chinese hamster ovary cell lines expressing human GPR8 and cloned the cDNA encoding its precursor protein. The cDNA encodes two forms of the peptide ligand with lengths of 23 and 30 amino acid residues as mature peptides. We designated the two ligands neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30). The amino acid sequence of NPW23 is completely identical to that of the N-terminal 23 residues of NPW30. Synthetic NPW23 and NPW30 activated and bound to both GPR7 and GPR8 at similar effective doses. Intracerebroventricular administration of NPW23 in rats increased food intake and stimulated prolactin release. These findings indicate that neuropeptide W is the endogenous ligand for both GPR7 and GPR8 and acts as a mediator of the central control of feeding and the neuroendocrine system. Searches for ligands for orphan G-protein-coupled receptors (GPCRs)1 have discovered many novel peptides and have identified the previously unknown receptors of bioactive substances (1-9). Studies on the newly identified ligands and their receptors have given us a more precise understanding of the physiological processes involved in the endocrine, cardiovascular, reproductive, immune, inflammatory, digestive, metabolic, and central nervous systems (1-11). In addition, these studies have provided opportunities to discover innovative drugs that exert their pharmacological effects by interacting with an identified receptor as an agonist or antagonist (12). GPR7 and GPR8, for which the ligands have not been identified, are structurally related orphan GPCRs. Two genes for GPR7 and GPR8 were originally isolated from human genomic DNA by O'Dowd et al. (13). Human GPR7 highly resembles human GPR8, with an amino acid identity of 64%. Among various families of GPCRs, GPR7 and GPR8 share high similarity to the opioid and somatostatin receptor families. In mammalian brain, gene expression of GPR7 and GPR8 was detected by Northern blot and in situ hybridization analyses (13). Especially in rat brain, GPR7 mRNA was detected in regions of the cortex, hippocampus, and hypothalamus (14). Profiles of GPR7 and GPR8 expressed mainly in brain suggest that the endogenous ligands for the two receptors have several functions in the central nervous system.In this study, we report the purification, cloning, and characterization of neuropeptide W (NPW). We attempted to purify the agonist peptide for GPR8. The cDNA encoding the agonist peptide for GPR8 demonstrates the existence of neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30), which exhibit no meaningful similarity to any known peptides. With the functional and binding characterization of NPW for GPR7 and GPR8, we show that NPW is the endogenous ligand for both of these recept...

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“…genes involved in apoptosis like c-myc , Apaf-1 (Coldwell et al, 2000), XIAP (Holcik & Korneluk, 2000). The VEGF gene contains two IRESs in 5'UTR (Meiron et al, 2001). Very important role in translation initiation plays the nucleotide sequence flanking start codon with following sequence: GCCRCCAUGG.…”

Section: Insulin Resistance and Obesitymentioning

confidence: 99%

The Role of Single Nucleotide Polymorphisms of Untranslated Regions (Utrs) in Insulin Resistance Pathogenesis in Patients with Type 2 Diabetes

Małodobra¹

2011

Medical Complications of Type 2 Diabetes

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New Isoforms of VEGF Are Translated from Alternative Initiation CUG Codons Located in Its 5′UTR

Cited by 56 publications

References 25 publications

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

Identification of Neuropeptide W as the Endogenous Ligand for Orphan G-protein-coupled Receptors GPR7 and GPR8

The Role of Single Nucleotide Polymorphisms of Untranslated Regions (Utrs) in Insulin Resistance Pathogenesis in Patients with Type 2 Diabetes

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