RESUMO
C2H2 zinc-finger motif presents in 3% of proteins that are encoded in the human genome, and has the abilities to recognize DNA, RNA and protein. With nearly 3 decades of efforts, the mechanisms of zinc-finger mediated biomolecule recognitions have been studied to various extents. Zinc-finger binds into the major groove of DNA double helix, establishes an one-to-one recognition format between DNA bases and certain amino acids in a zinc-finger, and achieves specificity based on DNA sequences. While RNA molecules show a large variety in their structures, zinc-finger recognizes RNA through the collected information of specially displayed bases and special backbone folding. Initial studies have been performed on zinc-finger mediated protein-protein interactions. Existing data indicate multiple recognition modes. The studies on molecular mechanism have supported the development of engineered zinc-fingers, which have been introduced into applications. For its wide existence, large functional diversity and potential in translational applications, zinc-finger deserves a systematic study in every aspect.
Assuntos
Animais , Humanos , Sequência de Aminoácidos , Sítios de Ligação , DNA , Química , Genética , Fator de Transcrição Ikaros , Química , Genética , Proteínas Nucleares , Química , Genética , Ligação Proteica , Proteínas , Química , Genética , RNA Ribossômico 5S , Química , Genética , Fator de Transcrição TFIIIA , Química , Genética , Fatores de Transcrição , Química , Genética , Proteínas de Transporte Vesicular , Química , Genética , Dedos de ZincoRESUMO
Glaucomas comprise a group of hereditary optic neuropathies characterized by progressive and irreversible visual field loss and damage to the optic nerve head. It is a complex disease with multiple molecular mechanisms underlying its pathogenesis. Genetic heterogeneity is the hallmark of all glaucomas and multiple chromosomal loci have been linked to the disease, but only a few genes have been characterized, viz. myocilin (MYOC), optineurin (OPTN), WDR36 and neurotrophin-4 (NTF4) in primary open angle glaucoma (POAG) and CYP1B1 and LTBP2 in congenital and developmental glaucomas. Case-control-based association studies on candidate genes involved in different stages of glaucoma pathophysiology have indicated a very limited involvement. The complex mechanisms leading to glaucoma pathogenesis indicate that it could be attributed to multiple genes with varying magnitudes of effect. In this review, we provide an appraisal of the various efforts in unraveling the molecular mystery in glaucoma and also some future directions based on the available scientific knowledge and technological developments.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Autoanticorpos/imunologia , Morte Celular , Mapeamento Cromossômico , Proteínas do Sistema Complemento/imunologia , Sistema Enzimático do Citocromo P-450/genética , Proteínas do Citoesqueleto/genética , Epistasia Genética , Proteínas do Olho/genética , Expressão Gênica , Heterogeneidade Genética , Genoma Humano , Glaucoma/genética , Glaucoma/imunologia , Glaucoma/fisiopatologia , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Humanos , Fatores de Crescimento Neural/genética , Hipertensão Ocular/etiologia , Células Ganglionares da Retina , Fatores de Risco , Fator de Transcrição TFIIIA/genéticaRESUMO
Os viroides, apesar de serem constituídos por um pequeno RNA de fita simples, fortemente estruturado, circular, que não codifica proteínas, são capazes de se replicar de maneira autônoma em plantas superiores e causar doença interagindo diretamente com fatores do hospedeiro. Nesta revisão, serão apresentados e discutidos alguns dos mais recentes trabalhos envolvendo a interação de viroides com fatores do hospedeiro, incluindo aspectos relacionados à replicação, movimento e patogênese, além de suas características evolutivas. Nos últimos anos, alguns grupos de pesquisa têm se aventurado na busca por fatores do hospedeiro e mecanismos moleculares relacionados ao ciclo infeccioso dos viroides, tentando desvendar como esses pequenos RNAs interagem com o hospedeiro induzindo sintomas. Os viroides não codificam proteínas supressoras de silenciamento e, portanto, devem garantir sua existência utilizando estratégias baseadas em sua estrutura secundária, na compartimentalização em organelas, associação com fatores do hospedeiro e eficiência na replicação. A complexidade do ciclo infeccioso desses minúsculos RNAs indica que muitas interações desses patógenos com fatores do hospedeiro ainda devem ser identificadas.
Viroids are small, single-stranded, highly structured, circular RNAs that replicate autonomously in their hosts, without messenger RNA activity. Because they do not encode for proteins, viroids have to interact directly with host factors. This review presents recent progress in understanding the possible role of recently identified viroid-binding host proteins related to replication, trafficking and pathogenesis. It also discusses some aspects on viroid evolution. In recent years, efforts to understand how viroids replicate, cause disease and induce symptoms have prompted details on molecular mechanisms related to the viroid infectious cycle. Inasmuch as viroids lack protein-encoding capacity, including suppressors of gene silencing, their existence could be ensured by their compact conformation, compartimentalization in organelles, association with host factors or by their highly efficient replication. The complexity of the infectious cycle of these tiny pathogenic RNAs indicates that several interactions with host factors remain to be identified.
Assuntos
Viroides/ultraestrutura , RNA Mensageiro , Fator de Transcrição TFIIIA/análise , Interferência de RNA , Interações Hospedeiro-PatógenoRESUMO
Glaucoma is the second largest blinding disorder, after cataract, affecting about 67 million people worldwide. In India about 1.5 million people are blind due to glaucoma. Primary open angle glaucoma is the major sub-type of glaucoma affecting all ages and is genetically complex. Myocilin and optineurin are two different genes that have been implicated for primary open angle glaucoma. This review is focused on the studies being conducted in India on primary open angle glaucoma to identify the molecular defects and new directions undertaken using bioinformatic approaches towards a better understanding of the disease.