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Order Sobelivirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Figure 28.2 shows the genomic structure of the two families of the Sobelivirales order. The genome of the Solemoviridae family comprises a polycistronic, positive-sense, single-stranded RNA molecule of 4–4.6 kb. The genome organization is conserved, with 4–5 ORFs. The protein VPg is covalently attached to the 5′-terminus of viral and subviral RNAs, interacts with the translation initiation complex, and regulates the activity of viral protease and viral RNA-directed RNA polymerase (RdRP), expressed by means of ribosomal frameshifting. The two variants of the polyprotein are translated via a ribosomal leaky scanning mechanism from genomic RNA, and they undergo proteolytic processing at conserved cleavage sites between the domains. The coat protein (CP) is translated from the subgenomic RNA. The 3′-terminus is nonpolyadenylated but has a stable stem-loop or tRNA-like structure (Sõmera et al. 2021).
Small, but mighty? Searching for human microproteins and their potential for understanding health and disease
Published in Expert Review of Proteomics, 2018
Annie Rathore, Thomas F. Martinez, Qian Chu, Alan Saghatelian
Pioneering studies of protein translation initiation first identified the presence of smORFs in the 5ʹ-untranslated regions (UTRs) of some mRNAs, which are commonly referred to as upstream open reading frames (uORFs) [4]. uORFs regulate the translation of downstream ORFs by engaging the ribosome before it initiates at the downstream ORF. Translation of downstream ORF is thought to occur through leaky scanning, whereby the first uORF initiation site is skipped, or by reinitiation of ribosome scanning upon reaching the end of the uORF [4]. Though initially thought to be unimportant, the translated sequence of the uORF was shown to matter in several cases. For instance, a uORF in the AdoMet carboxylase mRNA encodes a hexapeptide that when mutated effects the efficiency of translation repression of the downstream AdoMet carboxylase ORF [5]. This observation demonstrated that in some cases it is the interaction between the translated peptide and the ribosome that is mediating the activity of a uORF. More generally, this example and others like it show that uORFs/smORFs are translated and that the microproteins they encode are biologically active, providing the first evidence for functional microproteins. Since these findings smORFs have been identified in other noncoding regions [1], including 3ʹ-UTR and RNAs that were thought to be noncoding.
Delayed O-methylation of l -DOPA in MB-COMT-deficient mice after oral administration of l -DOPA and carbidopa
Published in Xenobiotica, 2018
Anne Tammimäki, Anu Aonurm-Helm, Pekka T. Männistö
Catechol-O-methyltransferase (COMT) catalyzes the conversion of catecholamines and other catechols, e.g. l-DOPA and catechol estrogens, into their O-methylated metabolites using S-adenosyl-l-methionine as the methyl donor (Guldberg & Marsden, 1975; Männistö & Kaakkola, 1999). The COMT gene (COMT) codes for two isoforms of the COMT enzyme protein, soluble (S-COMT), and membrane-bound (MB-COMT) (Lundström et al., 1991; Salminen et al., 1990). The latter protein is slightly larger because it incorporates 50 additional hydrophobic amino acids that form the membrane anchor (Lundström et al., 1991; Bertocci et al., 1991). COMT contains six exons, the first two of which are non-coding. In exon 3, there are two AUG start codons for two promoters that control the expression of the two COMT transcripts (Tenhunen et al., 1994). The distal P2 promoter regulates the synthesis of a 1.5-kb transcript in humans. Based on the leaky scanning mechanism of translation initiation, this longer transcript can code for both S-COMT and MB-COMT proteins (Tenhunen & Ulmanen, 1993; Tenhunen et al., 1993,1994). The P1 promoter almost completely overlaps exon 3 and falls between the S-COMT and MB-COMT ATG start codons, partially overlapping the MB-COMT coding sequence. Therefore, the shorter mRNA transcript (1.3 kb in humans) regulated by P1 only codes for the S-COMT protein.