FIG. 8.

Model explaining the roles of the THO complex, Sub2, and Tho1 in mRNP cotranscriptional mRNP biogenesis in different genetic backgrounds. (A) In wild-type cells, the THO complex would facilitate loading of the Sub2-Yra1 heterodimers onto the nascent mRNA. Numerous Sub2 molecules are recruited onto the mRNA molecule as it is extended, allowing the formation of an export-competent mRNP, which is exported by Mex67-Mtr2. (B) In the absence of a functional THO complex, Sub2 is not loaded properly onto the nascent mRNA and only a few molecules gain access to the RNA by a THO-independent low-affinity mechanism. As a consequence, an improperly assembled export-incompetent mRNP is generated, which could form DNA-RNA hybrids behind the elongating RNAPII. (C) In the absence of a functional THO complex, overexpression of Sub2 increases the probability of Sub2 or Sub2-Yra1 to directly bind to the nascent mRNA, bypassing the requirement of THO to assemble an export-competent mRNP. (D) Overexpression of the Tho1 hnRNP will allow loading of Tho1 onto the nascent mRNA in the absence of THO complex. An alternative export-competent mRNP molecule would be formed with the essential Sub2-Yra1 subunits loaded in a THO-independent manner. This would explain why sub2Δ, in contrast to THO null mutations, cannot be suppressed by multicopy THO1.