SSAT mRNA TRANSLATION REPRESSION AND ACTIVATION
AssigneeTemple University of the Commonwealth System of Higher Education
InventorsSalim Merali, Oscar Mauricio Perez Leal, Magid Abou-Gharbia, Wayne E. Childers
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Abstract
The invention provides an isolated nucleic acid having a sequence encoding a spermidine/spermine acetyltransferase (“SSAT”), wherein translation of an mRNA comprising the encoded SSAT has increased basal translation and increased stimulated translation, compared to a wild-type mRNA encoding SSAT. Methods of use for the nucleic acid are also provided. Methods and compositions are also provided for reducing ischemia-reperfusion injury in organs or tissue for transplantation.
Claims38
An isolated nucleic acid comprising a first sequence encoding the polypeptide of SEQ ID No. 1, wherein the nucleotide sequence encoding Arg142 of SEQ ID No. 1 is CGC.
An isolated nucleic acid comprising a first sequence encoding the amino acids 1-26 of SEQ ID No. 1 operably linked to a second sequence encoding amino acids 134-171 of SEQ ID No. 1, wherein the nucleotide sequence encoding Arg142 of SEQ ID No. 1 is CGC.
A method for identifying an agent that increases translation of an mRNA encoding spermidine/spermine acetyltransferase comprising the steps of:
- assessing the level of translation of an RNA in the absence of a candidate agent to obtain a reference level of translation, wherein the RNA is a nucleic acid comprising a first sequence encoding the polypeptide of SEQ ID No. 1, wherein the nucleotide sequence encoding Arg142 of SEQ ID No. 1 is CGC,
- assessing the level of translation of the RNA in the presence of the candidate agent to obtain a test level of translation,
- wherein the candidate agent is identified as an agent that increases translation if the test level of translation is greater than the reference level of translation.
A method for identifying an agent that decreases translation of an mRNA encoding spermidine/spermine acetyltransferase comprising the steps of:
- assessing the level of translation of an RNA in the absence of a candidate agent to obtain a reference level of translation, wherein the RNA is a nucleic acid comprising a first sequence encoding the polypeptide of SEQ ID No. 1, wherein the nucleotide sequence encoding Arg142 of SEQ ID No. 1 is CGC,
- assessing the level of translation of the RNA in the presence of the candidate agent to obtain a test level of translation,
- wherein the candidate agent is identified as an agent that decreases translation if the test level of translation is less than the reference level of translation.
A method for reducing ischemia-reperfusion injury in organs or tissue for transplantation, comprising contacting said organs or tissue with an effective amount of a composition comprising an agent that decreases translation of an mRNA encoding spermidine/spermine acetyltransferase, which agent has been identified to decrease said translation by the method comprising:
- assessing the level of translation of an RNA in the absence of the agent to obtain a reference level of translation, wherein the RNA is a nucleic acid comprising a first sequence encoding the polypeptide of SEQ ID No. 1, wherein the nucleotide sequence encoding Arg142 of SEQ ID No. 1 is CGC,
- assessing the level of translation of the RNA in the presence of the agent to obtain a test level of translation,
- wherein the agent is identified as an agent that decreases translation if the test level of translation is less than the reference level of translation.
A method for reducing ischemia-reperfusion injury in organs or tissue for transplantation comprising contacting organs or tissue with an effective amount of a composition comprising an agent that decreases translation of an mRNA encoding spermidine/spermine acetyltransferase, wherein said at least one agent is selected from the group consisting of astemizole, terfenadine, vanoxerine, suloctidil, digitoxigenin, digoxin, parthenolide, chrysene-1,4-quinone, sertindole, lanatoside C, beta-escin, alexidine, fluspirilen, thonzonium, toremifene, proscillaridin A, pyrvinium, aripiprazole, and pharmaceutically acceptable salts thereof.
A composition for preventing or treating ischemia-reperfusion injury in organs or tissue for transplantation comprising an organ preservation solution containing an effective amount of an agent that decreases translation of an mRNA encoding spermidine/spermine acetyltransferase in said organs or tissues, said agent selected from the group consisting of astemizole, terfenadine, vanoxerine, suloctidil, digitoxigenin, digoxin, parthenolide, chrysene-1,4-quinone, sertindole, lanatoside C, beta-escin, alexidine, fluspirilen, thonzonium, toremifene, proscillaridin A, pyrvinium, aripiprazole, and combinations thereof, and pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.