MATR3′s activity and mode of action are unclear, but its domains predict a role in RNA metabolism. We identified DHX9 and HNRNPK as new interactors of MATR3. DHX9 is a DNA and RNA helicase with diverse physiological functions in transcription, RNA processing, transport 
and translation 
. HNRNPK, a component of the heterogeneous nuclear ribonucleoprotein complex, is involved in chromatin remodeling and mRNA transcription, splicing and translation 
In view of the involvement of MATR3′s RRM domains and its new interactors in RNA metabolism, we asked whether RNA is involved in these interactions and found them to be dependent on both RNA and the RRM2 domain of MATR3. Furthermore, we obtained a first demonstration that MATR3 is an RNA-binding protein. Deep sequencing of bound RNA identified several small noncoding RNAs, which were over-represented in MATR3 immunoprecipitates and whose binding depended on MATR3′s RRM2 domain. Interestingly, one of these RNAs was 7SK, which is known to bind HNRNPK 
and DHX9 proteins 
. 7SK is a regulator of the P-TEFb kinase, which phosphorylates RNA polymerase II to promote transcription elongation 
. Thus, our data point to a protein complex containing MATR3, DHX9 and HNRNPK and the 7SK RNA. It is known that depletion of HNRNPK changes 7SK's interaction with its surrounding proteomic environment 
. In our experiments, depletion of MATR3 did not exert a similar effect (data not shown).
While HNRNPK was shown to co-activate p53, our microarray analysis indicated that MATR3 is not involved in p53 activation (Fig. S1
). However, MATR3 depletion led to decreased amounts of 77 mRNAs (). MATR3 binding of 9 transcripts of this group () was further validated (), and further experiments suggested that MATR3 is involved in controlling the levels of these transcripts by affecting their stability ().
The half-life of mRNA molecules is affected by specific sequences usually located in the 3′ UTR, and is regulated by RNA-binding proteins that bind to these sequences (48,49). An extensively documented example is the ARE sequence, a short sequence (AUUUA) found in the 3′ UTR of many mRNAs (50,51). RNA-binding proteins such as the Hu proteins bind to this sequence and enhance the stability of the corresponding mRNAs (52,53). The steady-state levels of the mRNAs thus depend on the balance between their own production and the levels and activity of proteins that stabilize them or enhance their degradation.
The levels of cellular MATR3 are highly regulated 
. We suggest that this tightly regulated protein stabilizes a number of transcripts, probably via direct interaction with these RNA species. We also propose that MATR3 is part of a protein complex containing, among others, the DHX9 and HNRNPK proteins as well as small noncoding RNAs such as 7SK. DHX9 and HNRNPK as well as the 7SK RNA were previously found to be involved in transcription and several RNA processes such as splicing 
. Identification of MATR3 as another player in this complex might shed light on new roles of MATR3 in RNA metabolism.