ABSTRACT
All organisms encode transfer RNAs (tRNAs) that are synthesized as precursor molecules bearing extra sequences at their 5' and 3' ends; some tRNAs also contain introns, which are removed by splicing. Despite commonality in what the ultimate goal is (i.e., producing a mature tRNA), mechanistically, tRNA splicing differs between Bacteria and Archaea or Eukarya. The number and position of tRNA introns varies between organisms and even between different tRNAs within the same organism, suggesting a degree of plasticity in both the evolution and persistence of modern tRNA splicing systems. Here we will review recent findings that not only highlight nuances in splicing pathways but also provide potential reasons for the maintenance of introns in tRNA. Recently, connections between defects in the components of the tRNA splicing machinery and medically relevant phenotypes in humans have been reported. These differences will be discussed in terms of the importance of splicing for tRNA function and in a broader context on how tRNA splicing defects can often have unpredictable consequences.
Subject(s)
Models, Genetic , RNA Splicing , RNA, Transfer/chemistry , Animals , Archaea/genetics , Bacteria/genetics , Endonucleases/physiology , Introns/physiology , Phosphotransferases/physiology , RNA, Transfer/metabolism , RNA, Transfer/physiology , Vertebrates/geneticsABSTRACT
Cockayne is a segmental progeroid syndrome that has autosomal recessive inheritance pattern. It is mainly characterized by Intrauterine growth retardation, severe postnatal growth deficiency, cachectic dwarfism, microcephaly, wizened face, sensorineural hearing loss, cataracts, dental caries, cardiac arrhythmias, hypertension, atherosclerosis, proteinuria, micropenis, renal failure, skeletal abnormalities, skin photosensitivity, decreased subcutaneous adipose tissue, cerebral atrophy, dementia, basal ganglia calcifications, ataxia and apraxia. It has a complex phenotype given by genetic heterogeneity. There are five gene responsible for this syndrome: CSA, CSB, XPB, XPD and XPG, in which various mutations have been found. The biochemical effect of these mutations includes dysfunctional protein of the repair system for oxidative damage to DNA, the complex coupled to transcription and the nucleotide excision repair system. Considering the role played for these proteins and its effects on clinical phenotype when they are deficient, we suggest that these genes might be candidates for analyzing susceptibility to common chronic degenerative diseases related to oxidative stress and aging.
Subject(s)
Cockayne Syndrome/genetics , DNA Damage , DNA Repair/genetics , Carbidopa/therapeutic use , Cockayne Syndrome/diagnosis , Cockayne Syndrome/drug therapy , Cockayne Syndrome/metabolism , Cockayne Syndrome/pathology , DNA Helicases/deficiency , DNA Helicases/genetics , DNA Helicases/physiology , DNA Repair Enzymes/deficiency , DNA Repair Enzymes/genetics , DNA Repair Enzymes/physiology , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Diagnosis, Differential , Endonucleases/deficiency , Endonucleases/genetics , Endonucleases/physiology , Genes, Recessive , Genetic Predisposition to Disease , Genotype , Growth Disorders/diagnosis , Humans , Levodopa/therapeutic use , Mutation , Nuclear Proteins/deficiency , Nuclear Proteins/genetics , Nuclear Proteins/physiology , Oxidative Stress/genetics , Phenotype , Photosensitivity Disorders/diagnosis , Poly-ADP-Ribose Binding Proteins , Transcription Factors/deficiency , Transcription Factors/genetics , Transcription Factors/physiology , Xeroderma Pigmentosum Group D Protein/deficiency , Xeroderma Pigmentosum Group D Protein/genetics , Xeroderma Pigmentosum Group D Protein/physiologyABSTRACT
The Bacillus subtilis enzymes ExoA and Nfo (originally termed YqfS) are endonucleases that can repair apurinic/apyrimidinic (AP) sites and strand breaks in DNA. We have analyzed how the lack of ExoA and Nfo affects the resistance of growing cells and dormant spores of B. subtilis to a variety of treatments, some of which generate AP sites and DNA strand breaks. The lack of ExoA and Nfo sensitized spores (termed alpha-beta-) lacking the majority of their DNA-protective alpha/beta-type small, acid-soluble spore proteins (SASP) to wet heat. However, the lack of these enzymes had no effect on the wet-heat resistance of spores that retained alpha/beta-type SASP. The lack of either ExoA or Nfo sensitized wild-type spores to dry heat, but loss of both proteins was necessary to sensitize alpha-beta- spores to dry heat. The lack of ExoA and Nfo also sensitized alpha-beta-, but not wild-type, spores to desiccation. In contrast, loss of ExoA and Nfo did not sensitize growing cells or wild-type or alpha-beta- spores to hydrogen peroxide or t-butylhydroperoxide. Loss of ExoA and Nfo also did not increase the spontaneous mutation frequency of growing cells. exoA expression took place not only in growing cells, but also in the forespore compartment of the sporulating cell. These results, together with those from previous work, suggest that ExoA and Nfo are additional factors that protect B. subtilis spores from DNA damage accumulated during spore dormancy.