Somatic Therapy of a Mouse SMA Model with a U7 snRNA Gene Correcting SMN2 Splicing

Splicing an mRNA precursor requires multiple factors involving five small nuclear RNA (snRNA) species called U1, U2, U4, U5, and U6. The presence of mRNA-type introns in the U6 snRNA genes of some yeasts led to the hypothesis that U6 snRNA may play a catalytic role in pre-mRNA splicing and that the U6 introns occurred through reverse splicing of an intron from an mRNA precursor into a catalytic site of U6 snRNA. We characterized the U2 snRNA gene of the yeast Rhodotorula hasegawae, which has four mRNA-type introns in the U6 snRNA gene, and found an mRNA-type intron of 60 bp. The intron of the U2 snRNA gene is present in the highly conserved region immediately downstream of the branch site recognition domain. Interestingly, we found that this region can form a novel base pairing with U6 snRNA. We discuss the possible implications of these findings for the mechanisms of intron acquisition and for the role of U2 snRNA in pre-mRNA splicing.

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Depressive Disorders: Update on Diagnosis, Etiology, and Treatment

10.2310/tywc.1640 ◽

2018 ◽

Author(s):

Isabelle E. Bauer ◽

Antonio L Teixeira ◽

Marsal Sanches ◽

Jair C. Soares

Keyword(s):

Depressive Disorder ◽

Depressive Disorders ◽

Treatment Strategies ◽

Premenstrual Dysphoric Disorder ◽

Brain Volumes ◽

Somatic Therapy ◽

Diagnostic And Statistical Manual ◽

Dsm 5 ◽

History Of ◽

Persistent Depressive Disorder

This review discusses the changes in the diagnostic criteria for depressive disorders as outlined in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), and recent findings exploring the etiology of and treatment strategies for these disorders. Depressive disorders are typically characterized by depression in the absence of a lifetime history of mania or hypomania. New developments in the DSM-5 include the recognition of new types of depressive disorders, such as disruptive mood dysregulation disorder, persistent depressive disorder, premenstrual dysphoric disorder, and the addition of catatonic features as a specifier for persistent depressive disorder. These diagnostic changes have important implications for the prognosis and treatment of this condition. A thorough understanding of both the clinical phenotype and the biosignature of these conditions is essential to provide individualized, long-term, effective treatments to affected individuals. This review contains 1 table and 52 references Key words: brain volumes, depressive disorders, DSM-5, hormones, inflammation, neuropeptides, somatic therapy, stress

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Interactions of U2 Gene Loci and Their Nuclear Transcripts with Cajal (Coiled) Bodies: Evidence for PreU2 within Cajal Bodies

Molecular Biology of the Cell ◽

10.1091/mbc.11.9.2987 ◽

2000 ◽

Vol 11 (9) ◽

pp. 2987-2998 ◽

Cited By ~ 40

Author(s):

Kelly P. Smith ◽

Jeanne Bentley Lawrence

Keyword(s):

Potential Role ◽

Coiled Body ◽

Oligonucleotide Probes ◽

Primary Transcript ◽

U2 Snrna ◽

Rna Foci ◽

Coiled Bodies ◽

Snrna Gene

The Cajal (coiled) body (CB) is a structure enriched in proteins involved in mRNA, rRNA, and snRNA metabolism. CBs have been shown to interact with specific histone and snRNA gene loci. To examine the potential role of CBs in U2 snRNA metabolism, we used a variety of genomic and oligonucleotide probes to visualize in situ newly synthesized U2 snRNA relative to U2 loci and CBs. Results demonstrate that long spacer sequences between U2 coding repeats are transcribed, supporting other recent evidence that U2 transcription proceeds past the 3′ box. The presence of bright foci of this U2 locus RNA differed between alleles within the same nucleus; however, this did not correlate with the loci's association with a CB. Experiments with specific oligonucleotide probes revealed signal for preU2 RNA within CBs. PreU2 was also detected in the locus-associated RNA foci, whereas sequences 3′ of preU2 were found only in these foci, not in CBs. This suggests that a longer primary transcript is processed before entry into CBs. Although this work shows that direct contact of a U2 locus with a CB is not simply correlated with RNA at that locus, it provides the first evidence of new preU2 transcripts within CBs. We also show that, in contrast to CBs, SMN gems do not associate with U2 gene loci and do not contain preU2. Because other evidence indicates that preU2 is processed in the cytoplasm before assembly into snRNPs, results point to an involvement of CBs in modification or transport of preU2 RNA.

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