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1.
Trends Parasitol ; 35(10): 778-794, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31473096

RESUMO

Trypanosomatids are protozoan parasites that cycle between an insect and a mammalian host. The large-subunit rRNA of these organisms undergoes unique processing events absent in other eukaryotes. Recently, small nucleolar RNAs (snoRNAs) that mediate these specific cleavages were identified. Trypanosomatid rRNA is rich in RNA modifications such as 2'-O-methylation (Nm) and pseudouridylation (Ψ) that are also guided by these snoRNAs. A subset of these modifications is developmentally regulated and increased in the parasite form that propagates in the mammalian host. Such hypermodification contributes the temperature adaptation and hence infectivity during cycling of the parasite. rRNA processing and modification should be considered promising drug targets for fighting the diseases caused by these parasites.


Assuntos
RNA de Protozoário/biossíntese , Trypanosomatina/fisiologia , Sistemas de Liberação de Medicamentos , Infecções por Euglenozoa/tratamento farmacológico , Infecções por Euglenozoa/parasitologia , Humanos , Processamento Pós-Transcricional do RNA
2.
Nucleic Acids Res ; 47(5): 2609-2629, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30605535

RESUMO

In trypanosomes, in contrast to most eukaryotes, the large subunit (LSU) ribosomal RNA is fragmented into two large and four small ribosomal RNAs (srRNAs) pieces, and this additional processing likely requires trypanosome-specific factors. Here, we examined the role of 10 abundant small nucleolar RNAs (snoRNAs) involved in rRNA processing. We show that each snoRNA involved in LSU processing associates with factors engaged in either early or late biogenesis steps. Five of these snoRNAs interact with the intervening sequences of rRNA precursor, whereas the others only guide rRNA modifications. The function of the snoRNAs was explored by silencing snoRNAs. The data suggest that the LSU rRNA processing events do not correspond to the order of rRNA transcription, and that srRNAs 2, 4 and 6 which are part of LSU are processed before srRNA1. Interestingly, the 6 snoRNAs that affect srRNA1 processing guide modifications on rRNA positions that span locations from the protein exit tunnel to the srRNA1, suggesting that these modifications may serve as check-points preceding the liberation of srRNA1. This study identifies the highest number of snoRNAs so far described that are involved in rRNA processing and/or rRNA folding and highlights their function in the unique trypanosome rRNA maturation events.


Assuntos
Processamento Pós-Transcricional do RNA/genética , RNA Ribossômico/genética , RNA Nuclear Pequeno/genética , Trypanosoma brucei brucei/genética , Conformação de Ácido Nucleico , Precursores de RNA/genética , Transcrição Gênica
3.
J Clin Epidemiol ; 61(6): 611-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18471666

RESUMO

OBJECTIVE: We compared agreement between child and parent responses to questions assessing prevalence of asthma and other severe respiratory symptoms. STUDY DESIGN AND SETTING: Fifth-grade children enrolled in public schools and their parents separately completed a health survey, which included respiratory symptom questions from the International Study of Asthma and Allergies in Childhood (ISAAC). Agreement on respiratory symptom questions was assessed with Cohen's Kappa coefficient. Asthma prevalence estimates based on responses to several questions were also compared using child and parent data. The analysis was based on a study sample size of 230 matched parent and child questionnaires. RESULTS: High levels of agreement (Kappa: 0.76 and 0.79) between child and parent responses were observed for current and lifetime asthma, and similar asthma prevalence estimates were obtained from child and parent response data. Five of the questions on potentially severe respiratory symptoms had low to fair levels of agreement (Kappa: -0.01 to 0.38), resulting in statistically significantly different prevalence estimates in three of the five symptoms. CONCLUSIONS: Separate parent and child responses to a series of respiratory symptom and asthma questions yielded similar estimates for asthma prevalence but different estimates for the prevalence of several severe respiratory symptoms.


Assuntos
Asma/epidemiologia , Asma/diagnóstico , Criança , Métodos Epidemiológicos , Inquéritos Epidemiológicos , Humanos , Maine/epidemiologia , Pais , Sons Respiratórios , Autorrevelação
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