Genome-wide analysis of mRNAs regulated by the THO complex in Drosophila melanogaster

Abstract

In yeast cells, the THO complex has been implicated in mitotic recombination, transcription elongation and mRNA nuclear export. The stable core of THO consists of Tho2p, Hpr1p, Mft1p and Thp2p. Whether a complex with similar functions assembles in metazoa has not yet been established. Here we report that Drosophila melanogaster THO consists of THO2, HPR1 and three proteins, THOC5-THOC7, which have no orthologs in budding yeast. Gene expression profiling in cells depleted of THO components revealed that <20% of the transcriptome was regulated by THO. Nonetheless, export of heat-shock mRNAs under heat stress was strictly dependent on THO function. Notably, 8% of upregulated genes encode proteins involved in DNA repair. Thus, although THO function seems to be conserved, the vast majority of mRNAs are transcribed and exported independently of THO in D. melanogaster.

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

“…At present, the role of the THO complex in the mammalian system is not clear. In the Drosophila system, it has been shown that THO complex is required for efficient export of only a few mRNAs (Rehwinkel et al, 2004). We demonstrate here that FMIP/THOC5 suppresses the mRNA processing/ export of C/EBPalpha.…”

“…On the other hand, C/EBPalpha is absolutely responsible for termination of mitotic clonal expansion in adipocyte differentiation (Zhang et al, 2004), whereas C/EBPbeta has been shown to be promitotic in this system (Tang et al, 2003). As stated above, THOC5 is a member of the nuclear export complex in D. melanogaster (Rehwinkel et al, 2004), and is the orthologue of FMIP. Indeed THOC1, a member of THO complex, was coimmunoprecipitated with FMIP, and the amount of THOC1/FMIP complex was increased in the presence of adipocyte differentiation medium (A Mancini and O El Bounkari, unpublished data).…”

“…On the other hand, in agreement with data obtained from morphological experiments (Figure 3), in FMIP knockdown cells, C/EBPalpha is expressed even in the presence of muscle differentiation medium (Figure 4c), suggesting that FMIP downmodulates polyadenylated C/EBPalpha mRNA expression under these conditions. C/EBPalpha counteracts the effect of FMIP on adipocyte/myocyte differentiation Recently, a mammalian homologue of THOC5 in Drosophila melanogaster which is a member of the nuclear export complex (Rehwinkel et al, 2004), was identified as fSAP79 (Masuda et al, 2005). The aminoacid sequence of fSAP79 is identical to FMIP.…”

“…However, the role of the THO complex in the mammalian system is not well studied. In the Drosophila system, it has been shown that THO is required for efficient export of only a few mRNA (Rehwinkel et al, 2004). Nevertheless, this raises the question whether the FMIP-induced phenotype is owing to C/EBPalpha protein alone or if additional proteins are involved.…”

An allelic series for studying the mouse Thoc1 gene

“…2005; Rehwinkel et al, 2004). Depletion of Thoc1 protein (pThoc1) from human or insect cells compromises transcriptional elongation and nuclear RNA export of some genes.…”