Matrin 3: Chromosomal distribution and protein interactions

Abstract

Matrin 3 (matr3), an abundant protein of the internal nuclear matrix, has been linked to a variety of functional events. As a step toward defining its multifunctional nature, we have studied the association of matr3 with chromosome territories and identified potential interacting proteins. A similar staining pattern of matr3 was observed in fixed WI38 fibroblast cells and in live HeLa cells using a matr3-GFP construct. Matr3 was detected throughout autosomal and the active X chromosome territories. Conversely, matr3 was strikingly excluded from the inactive X chromosome as well as within both the perinuclear and perinucleolar heterochromatin. Yeast two hybrid analysis identified matr3 interactions with 33 unique nuclear localized proteins and also revealed its propensity for self association. A majority of these proteins are involved in RNA metabolism and chromatin remodeling while others function in protein translation, DNA replication/repair and apoptosis. Further analysis of a selection of these proteins and scaffold attachment factor A (SAFA) by co-localization and co-immunoprecipitation experiments using HeLa cells confirmed their interactions with matr3.

The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins

“…Using the iCLIP assay, we have found that SAFB1 binds to several lncRNA transcripts (MALAT1, NEAT1, TUG1 and XIST), which have been linked to regulation of gene expression [43]. Both MALAT1 and NEAT1 have been found to associate with genes actively transcribing pre-mRNAs, predominantly around transcription termination sites [52,53], while TUG1, together with MALAT1, is involved in determining PRC2 function [54]. The silencing of an entire X chromosome during female development is orchestrated by XIST, which coats the inactive chromosome.…”

“…Conversely, weaker interactions may be maintained in the presence of low salt, but there may be a risk of artefactual interactions. [10], hnRNPC [10], hnRNPD [120], hnRNPG [25,84,121], hnRNPI [10], hnRNPK [10,122], hnRNPU [10] SR proteins SRSF1 [33], SRSF7 [26], SRSF9 [26,33], SREK1 [88], SRRM1 [123] SR protein kinase SRPK1 [89] Chromatin CHD1 [72], NCOR [37,71], HDAC3, [37,71] BRG1 [73], Matrin3 [54] Transcription RNAPolII [33], TAF II 68 [124], steroid receptors [67][68][69], P53 [70] Miscellaneous PIAS1 [37], ZO-2 [125], Zbed4 [126] Also, co-immunoprecipitation does not distinguish between direct protein interactions and interactions mediated by 'bridging' molecules, such as other proteins or nucleic acids. Formation of homo-and hetero-dimers of SAFB1 and SAFB2, as well as interactions with several hnRNP proteins, has been observed (see Table 1 for a summary of some of the proteins shown to interact with SAFB proteins).…”

“…In addition to interactions with other RBPs and SR proteins, SAFB also binds to many proteins involved in transcription (including RNA polymerase and transcription factors, such as steroid receptors [67][68][69] and p53 [70]), as well as many proteins and protein complexes that play important roles in determining chromatin structure and function, such as NCOR and HDAC3 [37,71], CHD1 [72], BRG1 [73] and matrin3 [54].…”

“…Thus, appropriate sub-nuclear localisation of Pit1 mediated by a SAP domain seems to be essential for Pit1 function. Both SAFB and matrin-3 have long been recognised as core scaffold matrix proteins, and co-localisation of the two proteins has been demonstrated [54]. At first sight, it may seem surprising that SAFB can exert both repressive and positive effects by what appear to be similar mechanisms, but another study by the Rosenfeld group might indicate some of the processes which could be involved [83].…”

Matrin 3 Augments the Transcriptional Activity of an SV40 Promoter-Mediated Luciferase Gene with a Highly Repetitive DNA Component

“…Matrin 3, an abundant protein of the internal nuclear matrix, has been linked to a variety of functional events. Zeitz et al have reported that matrin 3 interacts with 33 unique nuclear localized proteins and also revealed its propensity for self-association [23].…”