Sandbox Reserved 1085

Endoribonuclease III is a class 1 RNase III hydrolase enzyme. In general its function, which seems to be universally conserved, is the binding to and cleavage of dsRNA. Endoribonuclease III appears to be crucial for an organisms ability to rapidly adapt to environmental changes through dsRNA processing and decay.

Universally, it has been shown to mediate RNA turnover at the post-transcriptional level through processing rRNAs, tRNAs, some mRNAs, as well as non-coding dsRNAs. In microbes, RNase III has been shown that it also represses the synthesis of virulence factors (through the cleavage of foreign RNA.) ^[1]

In eukaryotes, RNase III has also been shown to generate microRNAs and siRNAs, which are central to gene regulation pathways.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[2] or to the article describing Jmol ^[3] to the rescue.

RNase III (1O0W)

Exploring the Structure

Structure The monomer of Aquifex aeolicus RNase III (Aa-RNase III) are composed of an endonuclease domain (endoND) and a dsRNA binding domain (dsRBD)[1]. The sequence of the endoND is characterized by a stretch of conserved residues (37ERLEFLGD44 in Aa-RNase III), which is known as the RNase III signature motif and makes up a large part of the active center. RNase III can affect gene expression in either of two ways: as a processing enzyme which RNase III cleaves both natural and synthetic dsRNA into small duplex products averaging 10–18 base pairs in length, or as a binding protein which binds and stabilizes certain RNAs, thus suppressing the expression of certain genes[2, 3].

On the basis of the structural and biochemical data, catalytic models were proposed before the structure of a catalytic complex became available. The crystal structure shows that Aa-RNase III is composed of a symmetric dimer. In addition, in vivo data suggested that E110, E37, D44, and E64 are essential for catalysis[4]. This led to the model of the proteins active centers, which can accommodate a dsRNA substrate, each containing two different RNA cleavage sites, D44/E110 and E37/E64. Specifically, E64 from each partner subunit, along with E37, E40, and D44 are located in the signature motif located at each end of a valley-like cleft[5]. Comparing the structure of Aa-RNase III with the structure of RNA-free Thermotoga maritima RNase III (RNA-free Tm-RNase III, PDB ID code 1O0W)[6] shows that there is dramatic rotation and shift of dsRBD due to RNA binding.

A Hypothetical Pathway Leading to the two Functional Forms of RNase III

A Hypothetical Pathway Leading to the two Functional Forms of RNase III Catalytic processes in addition to the catalytic and noncatalytic forms of the Aa-RNase III–dsRNA structures revealed possible intermediate states of dsRNA binding and a hypothetical pathway of RNase III in vivo. The RNA-free RNase III dimer in conformation A (Figure a, PDB 1O0W) first binds a dsRNA with one of the two dsRBDs. The resulting complex may have at least two possible conformations, B (Figure b, PDB1YZ9 AaRNase IIIE110Q) and E (Figure e, PDB 1YYO), in which the dsRNA is located outside of the catalytic valley. These two conformations, b and e, appear to be interchangeable. In conformation E, the two dsRBDs pack against each other, hindering free rotation of the dsRBD-dsRNA complex around the flexible linker between the endoND and dsRBD. Conformation b allows free rotation of dsRBD-dsRNA around the linker (Figure b). The clockwise rotation of dsRBD-dsRNA leads to the catalytic form (Figure d, PDB 2EZ6) via conformation C (Figure c, PDB 1YYW). Conformations B and C are also likely to be interchangeable. In contrast, a factor that uncouples binding and processing can further stabilize conformation E leading to the noncatalytic form of RNase III (Figure f, PDB 1RC7)[4, 6, 7].

Function

Disease

Relevance

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