Genome-wide Analysis Identifies Interleukin-10 mRNA as Target of Tristetraprolin

Tristetraprolin (TTP) is an RNA-binding protein required for the rapid degradation of mRNAs containing AU-rich elements. Targets regulated by TTP include the mRNAs encoding tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, interleukin-2 (IL-2), and immediate early response 3. To identify novel target mRNAs of TTP in macrophages, we used a genome-wide approach that combines RNA immunoprecipitation and microarray analysis. A list was compiled of 137 mRNAs that are associated with TTP with an estimated accuracy on the order of 90%. Sequence a of AU-rich with in and in of that is a novel target regulated by of a in the of for of RNA-binding Tristetraprolin (TTP) is an RNA-binding protein required for the rapid degradation of mRNAs containing AU-rich elements. Targets regulated by TTP include the mRNAs encoding tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, interleukin-2 (IL-2), and immediate early response 3. To identify novel target mRNAs of TTP in macrophages, we used a genome-wide approach that combines RNA immunoprecipitation and microarray analysis. A list was compiled of 137 mRNAs that are associated with TTP with an estimated accuracy on the order of 90%. Sequence a of AU-rich with in and in of that is a novel target regulated by of a in the of for of RNA-binding Tristetraprolin (TTP) used protein RNA tumor necrosis protein used protein RNA tumor necrosis protein is an RNA-binding protein that AU-rich are for a of mRNAs of TTP the rapid degradation of target target was by the of an by and of are in and with of the in a of a TTP was the of and rapid degradation of that TTP granulocyte-macrophage and interleukin-2 early response a novel target in of TTP by of TTP that the rapid degradation of and is on TTP in that TTP and that and TTP by TTP of TTP in was of and was in that of mRNAs in TTP the the of a of a genome-wide mRNAs with in is a in the of was a that the degradation of granulocyte-macrophage colony-stimulating of mRNAs a on the and of a a granulocyte-macrophage colony-stimulating factor, a of a and is the of the rapid an and is the that in TTP with in and a TTP are identify the of A of that of mRNAs containing a for identify mRNAs that are regulated the of an RNA RNA-binding immunoprecipitation and microarray the of mRNAs associated with RNA-binding and we used identify that with TTP in by that the and the are in of we that a of mRNAs is regulated by of TTP the of and that the and the of the for on in containing and and with and was by for the of and of the was the RNA was for with protein by and with for protein for and with of RNA was and was for a and an of RNA was the the RNA was and the was and was a and by in the was a and a was and in by and the was with that by a the of the was and was and the and and by of microarray and and by the in of the a was by the the RNA by the the A was for by the the RNA by the the A list was with that and and the was is on Sequence the on identify by an and by the of a the of the by the of A was for a for the was an in and is in the is is is a a by of AU-rich in the of RNA was for with in and mRNAs by with a of 137 mRNAs by and for the of the of of a the of the 137 mRNAs with in the of containing of is for the mRNAs in mRNAs in mRNAs the and of the and in with and with the the and of and and for in containing with and and was a of was used a of and was used a of and with and in by and used by and the for for for for for for for and for RNA by in and with the for for for protein for protein for for protein for and for protein are in and the was by and and a the of the was by and and a the of the was by and by and was a the of the was by and with and the was a the of are in in a of and containing with for the of for in was on a of the of TTP with associated for with the of by and for an that used mRNAs associated with and TTP was the of TTP was and a in the TTP is a protein for we a TTP was with TTP was with a was with the TTP RNA an in the that and is that mRNAs TTP and mRNAs RNA-binding that with of for with in was with TTP of TTP protein was by and was by RNA immunoprecipitation was in A that was used for of the was by of TTP and an RNA-binding and RNA and was by with that an of mRNAs by identify mRNAs on a genome-wide for with and RNA was the and the with the TTP To for the was used for the for the RNA and with of TTP was and the a was by the the by the the the with a of 137 mRNAs by analysis. mRNAs compiled in a list of mRNAs and the target mRNAs of TTP we the of the mRNAs for the of was that in and of an of of of the the is a TTP in of the and of the the a we the 137 mRNAs with the of the mRNAs an a in the and in the that are the is that the of the mRNAs are on of the mRNAs for a was with 137 mRNAs the the was in the of mRNAs A with in the of was the of the the of with was and with a of the that and are the mRNAs by the of the mRNAs is the of and in a of 137 the of on the the of is and the of a with a of is the of is and the of a with a of is the mRNAs a for and is in with the that and in are and for TTP of the list of we mRNAs and by analysis. mRNAs encoding and a of in of was and mRNAs and encoding protein protein and a of in used by the mRNAs for with in the of and we and for encoding and protein by the TTP in and was by that the of mRNAs in is on the order of of mRNAs associated with with in a of mRNAs in the of mRNAs encoding and was by analysis. RNA was with mRNAs encoding and mRNAs encoding and in A and in is for and and are of by and analysis. of mRNAs TTP was by for with include TTP mRNAs encoding and mRNAs by analysis. the list of 137 mRNAs and for TTP in the mRNAs are by is RNA was for with the of and for and for the of of a of mRNAs by TTP for we containing the of in the of the the and the an in with with the is a the and of was in the and of TTP a we the containing the of was and of TTP a we the was with was in the and of TTP the of and the in the and in the of that TTP the of the in a that the of and of mRNAs containing of the are in the is in the and the A of of the a and with and a RNA was with was by a of in the was for the containing the of the of the of the of and the of of mRNAs in the of mRNAs in To we the mRNAs for with TTP was in and a was in was in with with the of TTP in of the is in of and the in and and in that is of TTP the and mRNAs in and and mRNAs a in of mRNAs in and and and for and RNA was with for the the of the mRNAs encoding in the and the in the we the and we with and in and in in of mRNAs in and and and with and RNA was and the of was with and for and the of was with and for and by of the for and in A and the and the in the that in and is the of and the of in is that the of is the of by To for with in the of that the of the of in was in an that in is a of in a in we in for with a rapid in was in of that the in in a that is of the is for the of in that TTP on target by is in and for with with RNA was and was by analysis. of in and for with on a and and the was of and by we a genome-wide approach identify of we that are by of TTP in of a list of 137 mRNAs with and and of by and that list of mRNAs an accuracy on the order of list is the that is a target of TTP and with TTP is the in the and of the we the with a approach by a of is that mRNAs a of in a of the by To are we the the mRNAs the mRNAs in for with an that mRNAs encoding for in are the mRNAs with the that the mRNAs encoding and of are in the list of and with TTP in RNA with in a and rapid degradation that TTP of a by the of TTP the of and a TTP in for that are for that and are mRNAs is with a of 137 mRNAs with of a a by a of mRNAs the in and of the a of a a of an with the of is for mRNAs and for the the a the of is for mRNAs with the of mRNAs the of with and are of that and are the of of the the mRNAs that by in the mRNAs a was regulated by TTP of are by that are the TTP that in the of immediate early response and TTP the the in that TTP in a by a A was in of mRNAs TTP we that and TTP with TTP RNA-binding of was that the of mRNAs in the mRNAs was in and and mRNAs and a TTP mRNAs that are for we the that TTP of mRNAs containing the of and that TTP for and mRNAs in the of and and for the of that mRNAs degradation is on TTP granulocyte-macrophage colony-stimulating factor, and are by A an for immediate early response is in in is that of the mRNAs TTP RNA-binding is an with TTP the RNA-binding protein TTP degradation of a by with the mRNAs that the of and are by is that and mRNAs with RNA-binding that are the of that of TTP in a the degradation of the and mRNAs the that mRNAs are the of a that the of the the of an protein the of an is with in that are regulated by of RNA-binding in by RNA the of and for RNA-binding with for the of Tristetraprolin (TTP) used protein RNA tumor necrosis protein used protein RNA tumor necrosis protein is an RNA-binding protein that AU-rich are for a of mRNAs of TTP the rapid degradation of target target was by the of an by and of are in and with of the in a of a TTP was the of and rapid degradation of that TTP granulocyte-macrophage and interleukin-2 early response a novel target in of TTP by of TTP that the rapid degradation of and is on TTP in that TTP and that and TTP by TTP of TTP in was of and was in that of mRNAs in TTP the the of a of a genome-wide mRNAs with in is a in the of was a that the degradation of granulocyte-macrophage colony-stimulating of mRNAs a on the and of a a granulocyte-macrophage colony-stimulating factor, a of a and is the of the rapid an and is the that in TTP with in and a TTP are identify the of A of that of mRNAs containing a for identify mRNAs that are regulated the of an RNA RNA-binding immunoprecipitation and microarray the of mRNAs associated with RNA-binding and we used identify that with TTP in by that the and the are in of we that a of mRNAs is regulated by of TTP the of and that the and the of the for on in containing and and with and was by for the of and of the was the RNA was for with protein by and with for protein for and with of RNA was and was for a and an of RNA was the the RNA was and the was and was a and by in the was a and a was and in by and the was with that by a the of the was and was and the and and by of microarray and and by the in of the a was by the the RNA by the the A was for by the the RNA by the the A list was with that and and the was is on Sequence the on identify by an and by the of a the of the by the of A was for a for the was an in and is in the is is is a a by and in with and with the the and of and and for in containing with and and was a of was used a of and was used a of and with and in by and used by and the for for for for for for for and for RNA by in and with the for for for protein for protein for for protein for and for protein are in and the was by and and a the of the was by and and a the of the was by and by and was a the of the was by and with and the was a the of are in in a of and containing with for the of for in was on a for on in containing and and with and was by for the of and of the was the RNA was for with protein by and with for protein for and with of RNA was and was for a and an of RNA was the the RNA was and the was and was a and by in the was a and a was and in by and the was with that by a the of the was and was and the and and by of microarray and and by the in of the a was by the the RNA by the the A was for by the the RNA by the the A list was with that and and the was is on Sequence the on identify by an and by the of a the of the by the of A was for a for the was an in and is in the is is is a a by and in with and with the the and of and and for in containing with and and was a of was used a of and was used a of and with and in by and used by and the for for for for for for for and for RNA by in and with the for for for protein for protein for for protein for and for protein are in and the was by and and a the of the was by and and a the of the was by and by and was a the of the was by and with and the was a the of are in in a of and containing with for the of for in was on a of the of TTP with associated for with the of by and for an that used mRNAs associated with and TTP was the of TTP was and a in the TTP is a protein for we a TTP was with TTP was with a was with the TTP RNA an in the that and is that mRNAs TTP and mRNAs RNA-binding that with of mRNAs by identify mRNAs on a genome-wide for with and RNA was the and the with the TTP To for the was used for the for the RNA and with of TTP was and the a was by the the by the the the with a of 137 mRNAs by analysis. mRNAs compiled in a list of mRNAs and the target mRNAs of TTP we the of the mRNAs for the of was that in and of an of of of the the is a TTP in of the and of the the a we the 137 mRNAs with the of the mRNAs an a in the and in the that are the is that the of the mRNAs are on of the mRNAs for a was with 137 mRNAs the the was in the of mRNAs A with in the of was the of the the of with was and with a of the that and are the mRNAs by the of the mRNAs is the of and in a of 137 the of on the the of is and the of a with a of is the of is and the of a with a of is the mRNAs a for and is in with the that and in are and for TTP of the list of we mRNAs and by analysis. mRNAs encoding and a of in of was and mRNAs and encoding protein protein and a of in used by the mRNAs for with in the of and we and for encoding and protein by the TTP in and was by that the of mRNAs in is on the order of of mRNAs associated with with in a of mRNAs in the of mRNAs encoding and was by analysis. RNA was with mRNAs encoding and mRNAs encoding and in A and in is for and and are of by and analysis. of mRNAs TTP was by for with include TTP mRNAs encoding and mRNAs by analysis. the list of 137 mRNAs and for TTP in the mRNAs are by is RNA was for with the of and for and for the of of a of mRNAs by TTP for we containing the of in the of the the and the an in with with the is a the and of was in the and of TTP a we the containing the of was and of TTP a we the was with was in the and of TTP the of and the in the and in the of that TTP the of the in a that the of and of mRNAs containing of the are in the is in the and the A of of the a and with and a RNA was with was by a of in the was for the containing the of the of the of the of and the of of mRNAs in the of mRNAs in To we the mRNAs for with TTP was in and a was in was in with with the of TTP in of the is in of and the in and and in that is of TTP the and mRNAs in and and mRNAs a in of mRNAs in and and and for and RNA was with for the the of the mRNAs encoding in the and the in the we the and we with and in and in in of mRNAs in and and and with and RNA was and the of was with and for and the of was with and for and by of the for and in A and the and the in the that in and is the of and the of in is that the of is the of by To for with in the of that the of the of in was in an that in is a of in a in we in for with a rapid in was in of that the in in a that is of the is for the of in that TTP on target by is in and for with with RNA was and was by analysis. of in and for with on a and and the was of and by RNA of the of TTP with associated for with the of by and for an that used mRNAs associated with and TTP was the of TTP was and a in the TTP is a protein for we a TTP was with TTP was with a was with the TTP RNA an in the that and is that mRNAs TTP and mRNAs RNA-binding that with of mRNAs by identify mRNAs on a genome-wide for with and RNA was the and the with the TTP To for the was used for the for the RNA and with of TTP was and the a was by the the by the the the with a of 137 mRNAs by analysis. mRNAs compiled in a list of mRNAs and the target mRNAs of TTP we the of the mRNAs for the of was that in and of an of of of the the is a TTP in of the and of the the a we the 137 mRNAs with the of the mRNAs an a in the and in the that are the is that the of the mRNAs are on of the mRNAs To for a was with 137 mRNAs the the was in the of mRNAs A with in the of was the of the the of with was and with a of the that and are the mRNAs by the of the mRNAs is the of and in a of 137 the of on the the of is and the of a with a of is the of is and the of a with a of is the mRNAs a for and is in with the that and in are and for TTP of the list of we mRNAs and by analysis. mRNAs encoding and a of in of was and mRNAs and encoding protein protein and a of in used by the mRNAs for with in the of and we and for encoding and protein by the TTP in and was by that the of mRNAs in is on the order of 90%. of a of mRNAs by TTP for we containing the of in the of the the and the an in with with the is a the and of was in the and of TTP a we the containing the of was and of TTP a we the was with was in the and of TTP the of and the in the and in the of that TTP the of the in a that the of and of mRNAs in the of mRNAs in To we the mRNAs for with TTP was in and a was in was in with with the of TTP in of the is in of and the in and and in that is of TTP the and mRNAs in and and mRNAs a in To the we the and we with and in and in in the that in and is the of and the of in is that the of is the of by To for with in the of that the of the of in was in an that in is a of TTP in a in we in for with a rapid in was in of that the in in a that is of the is for the of in that TTP on target by we a genome-wide approach identify of we that are by of TTP in of a list of 137 mRNAs with and and of by and that list of mRNAs an accuracy on the order of list is the that is a target of TTP and with TTP is the in the and of the we the with a approach by a of is that mRNAs a of in a of the by To are we the the mRNAs the mRNAs in for with an that mRNAs encoding for in are the mRNAs with the that the mRNAs encoding and of are in the list of and with TTP in RNA with in a and rapid degradation that TTP of a by the of TTP the of and a TTP in for that are for that and are mRNAs is with a of 137 mRNAs with of a a by a of mRNAs the in and of the a of a a of an with the of is for mRNAs and for the the a the of is for mRNAs with the of mRNAs the of with and are of that and are the of of the the mRNAs that by in the mRNAs a was regulated by TTP of are by that are the TTP that in the of immediate early response and TTP the the in that TTP in a by a A was in of mRNAs TTP we that and TTP with TTP RNA-binding of was that the of mRNAs in the mRNAs was in and and mRNAs and a TTP mRNAs that are for we the that TTP of mRNAs containing the of and that TTP for and mRNAs in the of and and for the of that mRNAs degradation is on TTP granulocyte-macrophage colony-stimulating factor, and are by A an for immediate early response is in in is that of the mRNAs TTP RNA-binding is an with TTP the RNA-binding protein TTP degradation of a by with the mRNAs that the of and are by is that and mRNAs with RNA-binding that are the of that of TTP in a the degradation of the and mRNAs the that mRNAs are the of a that the of the the of an protein the of an is with in that are regulated by of RNA-binding in by RNA the of and for RNA-binding with for the of we a genome-wide approach identify of we that are by of TTP in of a list of 137 mRNAs with and and of by and that list of mRNAs an accuracy on the order of 90%. A list is the that is a target of TTP and with TTP is the in the and of the we the with a approach by a of A is that mRNAs a of in a of the by To are we the the mRNAs the mRNAs in for with an that mRNAs encoding for in are the mRNAs with the that the mRNAs encoding and of are in the list of and with TTP in RNA with in a and rapid degradation that TTP of a by the of TTP the of and a TTP in A for that are for that and are mRNAs is with a of 137 mRNAs with of a a by a of mRNAs the in and of the a of a a of an with the of is for mRNAs and for the the a the of is for mRNAs with the of mRNAs the of with and are of that and are the of of the the mRNAs that by in the mRNAs a was regulated by TTP of are by that are the TTP that in the of immediate early response and TTP the the in that TTP in a by a A was in of mRNAs TTP we that and TTP with TTP RNA-binding of was that the of mRNAs in the mRNAs was in and and mRNAs and a TTP mRNAs that are for we the that TTP of mRNAs containing the of and that TTP A for and mRNAs in the of and and for the of that mRNAs degradation is on TTP granulocyte-macrophage colony-stimulating factor, and are by A an for immediate early response is in in A is that of the mRNAs TTP RNA-binding is an with TTP the RNA-binding protein TTP degradation of a by with the mRNAs that the of and are by is that and mRNAs with RNA-binding that are the of that of TTP in a the degradation of the and mRNAs the that mRNAs are the of a that the of the the of an protein the of an is with in that are regulated by of RNA-binding in by RNA the of and for RNA-binding with for the of for the and for with with