Translational regulation of the rod photoreceptor cGMP-phosphodiesterase: the role of the 5'- and 3'-untranslated regions. 2006

Natik Piri, and Emmanuel Mendoza, and Jennifer Shih, and Clyde K Yamashita, and Novrouz B Akhmedov, and Debora B Farber
Jules Stein Eye Institute, UCLA, 100 Stein Plaza, Los Angeles, CA 90095, USA. piri@jsei.ucla.edu

We have established earlier that rod photoreceptor cGMP-phosphodiesterase (PDE6) alpha and beta subunits are equally represented in the retina at the protein level and have similar turnover rates. mRNA quantification revealed five PDE6beta messages for every PDE6alpha transcript pointing at post-transcriptional regulation of PDE6alpha and PDE6beta expression. Indeed, the wild-type PDE6alpha mRNA was translated 5-fold more efficiently than that of PDE6beta. The coding regions of these subunits had a major contribution in this process. Here, we extend our study of translational regulation of PDE6 subunits and present a detailed analysis of the role of PDE6alpha and PDE6beta 5'- and 3'-UTRs (untranslated regions) in this process. We showed that both the short and long PDE6beta 5'-UTRs lead to more efficient protein synthesis than the PDE6alpha 5'-UTR. The 3'-UTRs of PDE6alpha and PDE6beta stimulated translation by approximately 2- and 3-fold, respectively. However, the positive effect of the PDE6alpha or PDE6beta 3'-UTRs was not observed when these regions were placed in constructs containing the 5'-UTR of the corresponding PDE6 subunit. Furthermore, it appears that PDE6alpha 5'- and 3'-UTRs may be involved in a base pairing interaction that reduces the efficiency of protein synthesis. Finally, using progressive deletion analysis of the PDE6alpha 5'-UTR, we have identified several regions that have significant contribution in regulation of protein synthesis. Based on these and earlier published data, it can be stated that an equimolar level of PDE6alpha and PDE6beta synthesized from different amounts of mRNA (ratio of PDE6alpha to PDE6beta mRNA in the retina is 1:5) is achieved as a result of combinatorial effects of 5'-UTRs and coding regions of PDE6alpha and PDE6beta mRNAs on translational regulation.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014176 Protein Biosynthesis The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS. Genetic Translation,Peptide Biosynthesis, Ribosomal,Protein Translation,Translation, Genetic,Protein Biosynthesis, Ribosomal,Protein Synthesis, Ribosomal,Ribosomal Peptide Biosynthesis,mRNA Translation,Biosynthesis, Protein,Biosynthesis, Ribosomal Peptide,Biosynthesis, Ribosomal Protein,Genetic Translations,Ribosomal Protein Biosynthesis,Ribosomal Protein Synthesis,Synthesis, Ribosomal Protein,Translation, Protein,Translation, mRNA,mRNA Translations
D015106 3',5'-Cyclic-GMP Phosphodiesterases Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate. 3',5'-Cyclic GMP 5'-Nucleotidohydrolase,3',5'-Cyclic GMP Phosphodiesterase,3',5'-Cyclic-GMP Phosphodiesterase,3,5-Cyclic GMP 5-Nucleotidohydrolase,3,5-Cyclic GMP Phosphodiesterase,3',5' Cyclic GMP 5' Nucleotidohydrolase,3',5' Cyclic GMP Phosphodiesterase,3',5' Cyclic GMP Phosphodiesterases,3,5 Cyclic GMP 5 Nucleotidohydrolase,3,5 Cyclic GMP Phosphodiesterase,5'-Nucleotidohydrolase, 3',5'-Cyclic GMP,5-Nucleotidohydrolase, 3,5-Cyclic GMP,GMP 5'-Nucleotidohydrolase, 3',5'-Cyclic,GMP 5-Nucleotidohydrolase, 3,5-Cyclic,GMP Phosphodiesterase, 3',5'-Cyclic,GMP Phosphodiesterase, 3,5-Cyclic,Phosphodiesterase, 3',5'-Cyclic GMP,Phosphodiesterase, 3',5'-Cyclic-GMP,Phosphodiesterase, 3,5-Cyclic GMP,Phosphodiesterases, 3',5'-Cyclic-GMP
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D017353 Gene Deletion A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. Deletion, Gene,Deletions, Gene,Gene Deletions
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein
D017948 Retinal Rod Photoreceptor Cells Photosensitive afferent neurons located in the peripheral retina, with their density increases radially away from the FOVEA CENTRALIS. Being much more sensitive to light than the RETINAL CONE CELLS, the rod cells are responsible for twilight vision (at scotopic intensities) as well as peripheral vision, but provide no color discrimination. Photoreceptors, Rod,Retinal Rod Cells,Rod Photoreceptors,Rods (Retina),Retinal Rod,Retinal Rod Cell,Retinal Rod Photoreceptor,Retinal Rod Photoreceptors,Rod Photoreceptor Cells,Cell, Retinal Rod,Cell, Rod Photoreceptor,Cells, Retinal Rod,Cells, Rod Photoreceptor,Photoreceptor Cell, Rod,Photoreceptor Cells, Rod,Photoreceptor, Retinal Rod,Photoreceptor, Rod,Photoreceptors, Retinal Rod,Retinal Rods,Rod (Retina),Rod Cell, Retinal,Rod Cells, Retinal,Rod Photoreceptor,Rod Photoreceptor Cell,Rod Photoreceptor, Retinal,Rod Photoreceptors, Retinal,Rod, Retinal,Rods, Retinal
D020121 5' Untranslated Regions The sequence at the 5' end of the messenger RNA that does not code for product. This sequence contains the ribosome binding site and other transcription and translation regulating sequences. 5'UTR,Leader Sequences, mRNA,Leader mRNA Sequences,mRNA Leader Sequences,5' UTR,5' UTRs,5' Untranslated Region,5'UTRs,Leader Sequence, mRNA,Leader mRNA Sequence,Region, 5' Untranslated,Regions, 5' Untranslated,Sequence, Leader mRNA,Sequence, mRNA Leader,Sequences, Leader mRNA,Sequences, mRNA Leader,UTR, 5',UTRs, 5',Untranslated Region, 5',Untranslated Regions, 5',mRNA Leader Sequence,mRNA Sequence, Leader,mRNA Sequences, Leader

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