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キーワード:
Amino Acid Motifs/genetics; Base Sequence; Binding Sites/genetics; Cell Line, Tumor; DEAD-box RNA Helicases/metabolism; Gene Expression Profiling; HEK293 Cells; Humans; Immunoblotting; Immunoprecipitation; Neoplasm Proteins/metabolism; Nuclear Matrix-Associated Proteins/genetics/*metabolism; Oligonucleotide Array Sequence Analysis; Phosphoproteins/genetics/metabolism; Protein Binding; RNA/genetics/*metabolism; RNA Interference; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger/genetics/*metabolism; RNA, Small Untranslated/metabolism; RNA-Binding Proteins/genetics/*metabolism; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleoproteins/metabolism
要旨:
Matrin 3 (MATR3) is a highly conserved, inner nuclear matrix protein with two zinc finger domains and two RNA recognition motifs (RRM), whose function is largely unknown. Recently we found MATR3 to be phosphorylated by the protein kinase ATM, which activates the cellular response to double strand breaks in the DNA. Here, we show that MATR3 interacts in an RNA-dependent manner with several proteins with established roles in RNA processing, and maintains its interaction with RNA via its RRM2 domain. Deep sequencing of the bound RNA (RIP-seq) identified several small noncoding RNA species. Using microarray analysis to explore MATR3's role in transcription, we identified 77 transcripts whose amounts depended on the presence of MATR3. We validated this finding with nine transcripts which were also bound to the MATR3 complex. Finally, we demonstrated the importance of MATR3 for maintaining the stability of several of these mRNA species and conclude that it has a role in mRNA stabilization. The data suggest that the cellular level of MATR3, known to be highly regulated, modulates the stability of a group of gene transcripts.
