Disordered gambling among people with psychotic disorders: a systematic review.

Disorders of gambling are more common among the mentally ill, including in people with psychotic disorders. The aim of this study was to conduct a systematic review of the literature regarding the prevalence and correlates of gambling disorders in people with psychotic disorders. We systematically reviewed English-language literature through searches of six bibliographic databases, all run on 11 November 2022: Medline ALL, Embase, Emcare, APA PsycINFO, CINAHL and the Cochrane Library. Observational studies that reported the prevalence of gambling in psychotic disorders or psychosis among gamblers were included. Studies were critically appraised using the Joanna Briggs Institute Critical Appraisal Tools. Sixteen studies, including 1,116,103 participants, from across a range of settings, were included. Most studies were done on males and recruited participants with a mean age of 40 years. Most of the studies (n = 12) were cross-sectional, and the remaining were case control in design. Most of the studies rated fair in quality. The prevalence of gambling among psychotic population ranged from 0.32 to 19.3%, with the majority of the studies reporting rates between 6.4 and 17%. The rates were 5-25 times higher than in the general population. While there were no consistent associations found with socio-demographic indices, several studies reported an association between gambling behaviours and substance use disorder among those with psychotic illnesses. Our research suggests that clinicians should assess for comorbid gambling among those with psychotic illness, particularly in those with mood symptoms, impulsivity, and substance use disorders. Gambling can negatively impact on their financial and social situations. Future research should study specific strategies or therapies among those with comorbid gambling and psychotic disorders.

The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci.

UPF1 is an RNA helicase that is required for nonsense-mediated mRNA decay (NMD) in eukaryotes, and the predominant view is that UPF1 mainly operates on the 3'UTRs of mRNAs that are directed for NMD in the cytoplasm. Here we offer evidence, obtained from Drosophila, that UPF1 constantly moves between the nucleus and cytoplasm by a mechanism that requires its RNA helicase activity. UPF1 is associated, genome-wide, with nascent RNAs at most of the active Pol II transcription sites and at some Pol III-transcribed genes, as demonstrated microscopically on the polytene chromosomes of salivary glands and by ChIP-seq analysis in S2 cells. Intron recognition seems to interfere with association and translocation of UPF1 on nascent pre-mRNAs, and cells depleted of UPF1 show defects in the release of mRNAs from transcription sites and their export from the nucleus.

Visualization of the joining of ribosomal subunits reveals the presence of 80S ribosomes in the nucleus.

In eukaryotes the 40S and 60S ribosomal subunits are assembled in the nucleolus, but there appear to be mechanisms preventing mRNA binding, 80S formation, and initiation of translation in the nucleus. To visualize association between ribosomal subunits, we tagged pairs of Drosophila ribosomal proteins (RPs) located in different subunits with mutually complementing halves of fluorescent proteins. Pairs of tagged RPs expected to interact, or be adjacent in the 80S structure, showed strong fluorescence, while pairs that were not in close proximity did not. Moreover, the complementation signal is found in ribosomal fractions and it was enhanced by translation elongation inhibitors and reduced by initiation inhibitors. Our technique achieved 80S visualization both in cultured cells and in fly tissues in vivo. Notably, while the main 80S signal was in the cytoplasm, clear signals were also seen in the nucleolus and at other nuclear sites. Furthermore, we detected rapid puromycin incorporation in the nucleolus and at transcription sites, providing an independent indication of functional 80S in the nucleolus and 80S association with nascent transcripts.

Fluorescent protein tagging confirms the presence of ribosomal proteins at Drosophila polytene chromosomes.

Most ribosomal proteins (RPs) are stoichiometrically incorporated into ribosomal subunits and play essential roles in ribosome biogenesis and function. However, a number of RPs appear to have non-ribosomal functions, which involve direct association with pre-mRNA and transcription factors at transcription sites. The consensus is that the RPs found at these sites are off ribosomal subunits, but observation that different RPs are usually found together suggests that ribosomal or ribosomal-like subunits might be present. Notably, it has previously been reported that antibodies against 20 different RPs stain the same Pol II transcription sites in Drosophila polytene chromosomes. Some concerns, however, were raised about the specificity of the antibodies. To investigate further whether RPs are present at transcription sites in Drosophila, we have generated several transgenic flies expressing RPs (RpS2, RpS5a, RpS9, RpS11, RpS13, RpS18, RpL8, RpL11, RpL32, and RpL36) tagged with either green or red fluorescent protein. Imaging of salivary gland cells showed that these proteins are, as expected, abundant in the cytoplasm as well as in the nucleolus. However, these RPs are also apparent in the nucleus in the region occupied by the chromosomes. Indeed, polytene chromosome immunostaining of a representative subset of tagged RPs confirms the association with transcribed loci. Furthermore, characterization of a strain expressing RpL41 functionally tagged at its native genomic locus with YFP, also showed apparent nuclear accumulation and chromosomal association, suggesting that such a nuclear localization pattern might be a shared feature of RPs and is biologically important. We anticipate that the transgenes described here should provide a useful research tool to visualize ribosomal subunits in Drosophila tissues and to study the non-ribosomal functions of RPs.

The intergenic spacer of the Drosophila Adh-Adhr dicistronic mRNA stimulates internal translation initiation.

The eukaryotic ribosome normally cannot be recruited upstream of internal ORFs and therefore polycistronic mRNAs are not efficiently translated in eukaryotic cells. However, examples of dicistronic mRNAs have been reported in Drosophila and other eukaryotes, and it was proposed that the intergenic spacers might contain internal ribosome entry site (IRES) elements. Here we have investigated the translation mechanism of the dicistronic Adh-Adhr mRNA of Drosophila melanogaster. The data indicate that the full-length intergenic spacer strongly enhances translation of the internal ORF of dicistronic reporters, both in S2 cells and adult flies. Interestingly, transcripts derived from intron-containing constructs gave rise to higher translation yields, suggesting a link between pre-mRNA splicing and efficient internal translation initiation.

UPF1 P-body localization.

NMD (nonsense-mediated mRNA decay) is a mechanism that degrades transcripts containing PTCs (premature translation termination codons). NMD is a translation-associated process that is expected to take place throughout the cytoplasm. However, recent studies have indicated that the core NMD factors UPF1 (up-frameshift-1), UPF2 and UPF3 can associate with P-bodies (processing bodies), which are large cytoplasmic granules replete with proteins involved in general mRNA decay and related processes. It has been proposed that UPF1 directs PTC-containing mRNAs to P-bodies and triggers decay. Here, we discuss the link between P-bodies and NMD in view of recent studies that suggest that P-bodies are not required for NMD in Drosophila.