Nuclear export of metazoan replication-dependent histone mRNAs is dependent on RNA length and is mediated by TAP

Abstract

Replication-dependent histone mRNAs are the only metazoan mRNAs that are not polyadenylated, ending instead in a conserved stem–loop sequence. Histone pre-mRNAs lack introns and are processed in the nucleus by a single cleavage step, which produces the mature 3′ end of the mRNA. We have systematically examined the requirements for the nuclear export of a mouse histone mRNA using the Xenopus oocyte system. Histone mRNAs were efficiently exported when injected as mature mRNAs, demonstrating that the process of 3′ end cleavage is not required for export factor binding. Export also does not depend on the stem–loop binding protein (SLBP) since mutations of the stem–loop that prevent SLBP binding and competition with a stem–loop RNA did not affect export. Only the length of the region upstream of the stem–loop, but not its sequence, was important for efficient export. Histone mRNA export was blocked by competition with constitutive transport element (CTE) RNA, indicating that the mRNA export receptor TAP is involved in histone mRNA export. Consistent with this observation, depletion of TAP from Drosophila cells by RNAi resulted in the restriction of mature histone mRNAs to the nucleus.