Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colicin E5 is a tRNA-specific ribonuclease that recognizes and cleaves four tRNAs in Escherichia coli that contain the hypermodified nucleoside queuosine (Q) at the wobble position. Cells that produce colicin E5 also synthesize the cognate immunity protein (Im5) that rapidly and tightly associates with colicin E5 to prevent it from cleaving its own tRNAs to avoid suicide. We report here the crystal structure of Im5 in a complex with the activity domain of colicin E5 (E5-CRD) at 1.15A resolution. The structure reveals an extruded domain from Im5 that docks into the recessed RNA binding cleft in E5-CRD, resulting in extensive interactions between the two proteins. The interactions are primarily hydrophilic, with an interface that contains complementary surface charges between the two proteins. Detailed interactions in three separate regions of the interface account for specific recognition of colicin E5 by Im5. Furthermore, single-site mutational studies of Im5 confirmed the important role of particular residues in recognition and binding of colicin E5. Structural comparison of the complex reported here with E5-CRD alone, as well as with a docking model of RNA-E5-CRD, indicates that Im5 achieves its inhibition by physically blocking the cleft in colicin E5 that engages the RNA substrate.
 ...
PMID:Molecular basis of inhibition of the ribonuclease activity in colicin E5 by its cognate immunity protein. 1652 91

Colicin E5 is a ribonuclease that specifically cleaves tRNA(Tyr), tRNA(His), tRNA(Asn) and tRNA(Asp) of sensitive Escherichia coli cells by recognizing their anticodon sequences. Since all organisms possess universal anticodons of these tRNAs, colicin E5 was expected to potentially cleave eukaryotic tRNAs. Here, we expressed the active domain of colicin E5 (E5-CRD) in Saccharomyces cerevisiae and investigated its effects on growth. E5-CRD impaired growth of host cells by cleaving tRNA(Tyr), tRNA(His), tRNA(Asn) and tRNA(Asp) in S. cerevisiae, which is the same repertoire as that in E. coli. This activity of E5-CRD was inhibited by the co-expression of its cognate inhibitor (ImmE5). Notably, the growth impairment by E5-CRD was reversible; cells restored the colony-forming activity after suppression of the E5-CRD expression. This seems different from the sharp killing effect of E5-CRD on E. coli. These results may provide insights into the role and behaviour of cytosolic tRNAs on cell growth and proliferation.
 ...
PMID:Colicin E5 ribonuclease domain cleaves Saccharomyces cerevisiae tRNAs leading to impairment of the cell growth. 1915 Nov 2

The RNA exosome is an evolutionarily conserved, ribonuclease complex that is critical for both processing and degradation of a variety of RNAs. Cofactors that associate with the RNA exosome likely dictate substrate specificity for this complex. Recently, mutations in genes encoding both structural subunits of the RNA exosome and its cofactors have been linked to human disease. Mutations in the RNA exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are similar autosomal-recessive, neurodegenerative diseases. Mutations in the RNA exosome gene EXOSC2 cause a distinct syndrome with various tissue-specific phenotypes including retinitis pigmentosa and mild intellectual disability. Mutations in genes that encode RNA exosome cofactors also cause tissue-specific diseases with complex phenotypes. How mutations in these genes give rise to distinct, tissue-specific diseases is not clear. In this review, we discuss the role of the RNA exosome complex and its cofactors in human disease, consider the amino acid changes that have been implicated in disease, and speculate on the mechanisms by which exosome gene mutations could underlie dysfunction and disease.
 ...
PMID:The RNA exosome and RNA exosome-linked disease. 2909 21

The evolutionarily conserved RNA exosome is a multisubunit ribonuclease complex that processes and/or degrades numerous RNAs. Recently, mutations in genes encoding both structural and catalytic subunits of the RNA exosome have been linked to human disease. Mutations in the structural exosome gene EXOSC2 cause a distinct syndrome that includes retinitis pigmentosa, hearing loss, and mild intellectual disability. In contrast, mutations in the structural exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are related autosomal recessive, neurodegenerative diseases. In addition, mutations in the structural exosome gene EXOSC9 cause a PCH-like disease with cerebellar atrophy and spinal motor neuronopathy. Finally, mutations in the catalytic exosome gene DIS3 have been linked to multiple myeloma, a neoplasm of plasma B cells. How mutations in these RNA exosome genes lead to distinct, tissue-specific diseases is not currently well understood. In this chapter, we examine the role of the RNA exosome complex in human disease and discuss the mechanisms by which mutations in different exosome subunit genes could impair RNA exosome function and give rise to diverse diseases.
 ...
PMID:The RNA Exosome and Human Disease. 3325 26