Novel endoribonuclease

A ribonucleic acid and endonuclease technology, applied in hydrolase, cells modified by introducing foreign genetic material, recombinant DNA technology, etc.

Inactive Publication Date: 2012-04-25
TAKARA HOLDINGS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the function of this toxin has not been fully demonstrated, it has been suggested that CcdB and ParE control the replication of target DNA gyrase, and RelE and Doc control transcription (Non-Patent Documents 1 and 2)

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Example 1: Isolate DR0662 from Micrococcus radioresistant R1, isolate Mb2014c homologue from Mycobacterium bovis BCG and construct expression plasmid

[0068] The amino acid and nucleotide sequences of the polypeptides encoded by the DR0662 gene from Micrococcus radioduranus R1 and the Mb2014c homologue gene from Mycobacterium bovis BCG and their nucleotide sequences can be obtained from the NCBI database (accession numbers NP_294385 and NC_001263, and NP_855664 and NC_002945 ). Primer DR0662-F (SEQ ID NO: 5) and primer DR0062-R (SEQ ID NO: 6) were synthesized according to the relevant information of DR0662 nucleotide sequence and used for PCR reaction to amplify the DNA region encoding the entire polypeptide.

[0069]Micrococcus radiodurans R1 genomic DNA can be obtained from ATCC (ATCC No. 13939D). PCR was performed using Pyrobest DNA polymerase (Takara Bio) and 50 ng of genomic DNA from Micrococcus radiodurans R1 and primers DR0662-F and DR0662-R to obtain a 368-bp ...

Embodiment 2

[0071] Example 2: Preparation of the DR0662 polypeptide from Micrococcus radiodurans R1 and the Mb2014c homologue polypeptide from Mycobacterium bovis

[0072] Example 1 transforms Escherichia coli BL21 (DE3) (Novagen) with the obtained expression vector pET-DR0662 or pET-Mb2014cHlg, obtains Escherichia coli, pET-DR0662 / BL21 (DE3) and pET-Mb2014cHlg / BL21 (DE3) for expression ). pET-DR0662 / BL21(DE3) or pET-Mb2014cHlg / BL21(DEB) was cultured in 5 ml LB medium containing 100 ug / ml ampicillin at 37°C. When OD600nm reached 0.6, IPTG (Takara Bio) was added to a final concentration of 1 mM to induce expression of the polypeptide. The culture was stopped two hours after the initiation of the induction, and the cells were collected by centrifugation. Suspend the cells in 300 μl lysis buffer (50 mM NaH 2 PO 4 , 300mM NaCl, 10mM imidazole, pH 8.0), it was disrupted by a sonicator (Handy sonic, Tomy). 20 μl of Ni-NTA agarose (Qiagen) was added, the supernatant was collected by centrif...

Embodiment 3

[0073] Embodiment 3: Use oligoribonucleotide as substrate to identify the nucleotide sequence specificity of DR0662 polypeptide and Mb2014c homologue polypeptide

[0074] Oligoribonucleotides were synthesized and cleavage assays were performed to study the nucleotide sequence specificity of the ribonuclease activity of the DR0662 polypeptide obtained in Example 2 and the Mb2014c homologue polypeptide.

[0075] Seven oligoribonucleotides in SEQ ID NO: 8-14 were synthesized as substrates. Incubate at 37° C. for 30 minutes with 5 μl of a reaction mixture consisting of 10 μM of one of the above oligoribonucleotides, 2.5 ng / μl of the DR0662 polypeptide or Mb2014c homologue polypeptide obtained in Example 2, and 10 mM Tris-HCl (pH 7.5). The reaction product was electrophoresed with 20% denaturing acrylamide gel (20% acrylamide, 7M urea, 0.5×TBE buffer). After staining with SYBR GREEN II (Takara Bio), the fluorescence image was analyzed with a fluorescence image analyzer FMBIO II Mu...

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Abstract

A polypeptide having a novel endoribonuclease activity; a nucleic acid encoding the polypeptide; recombinant DNA having the nucleic acid therein; a transformant transformed with the recombinant DNA; a process for producing the polypeptide comprising the steps of cultivating the transformant and collecting the polypeptide from the culture; a process for producing a digest of single-stranded RNA comprising the step of reacting the polypeptide with the single-stranded RNA; and a method for the digestion of single-stranded RNA.

Description

technical field [0001] The invention relates to a new sequence-specific endoribonuclease which can be used in the field of genetic engineering. Background technique [0002] It has been reported that some prokaryotic plasmids have the function of post-isolation killing (PSK) host, and the plasmid is shed from the host to maintain the plasmid in the host. This plasmid has a toxin-antitoxin gene. Antitoxins bind to toxins in cells to inactivate toxins. Antitoxins are easily degraded by proteases. The result of the degradation of the antitoxin by protease is the activation of the stable toxin (Non-Patent Document 1). This toxin-antitoxin gene is also present in the chromosomes of most prokaryotes. They respond to various stresses and play a role in apoptosis. Although the function of this toxin has not been fully confirmed, it has been suggested that CcdB and ParE control the replication of target DNA gyrase, and RelE and Doc control transcription (Non-Patent Documents 1 a...

Claims

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Application Information

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Patent Type & AuthorityPatents(China)
IPC IPC(8): C12N15/09C12N1/15C12N1/19C12N1/21C12N5/10C12N9/22C12P19/30
CPCC12N9/22
Inventor岛田雅光高山正范浅田起代藏加藤郁之进
OwnerTAKARA HOLDINGS