mRNA recognition and packaging by the human transcription-export complex

Newly made messenger RNAs are processed and packaged into ribonucleoprotein complexes (mRNPs) and recognized by the essential transcription-export complex (TREX) for nuclear export(1,2). However, the mechanisms of mRNP recognition and three-dimensional organization are poorly understood(3). Here, we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the two-megadalton TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon-junction complexes. Exon-junction complexes can multimerize through ALYREF, suggesting a mechanism for mRNP organization. Endogenous mRNPs form compact ‘globules’ that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact, and protect mRNAs to promote their packaging for nuclear export. The mRNP globule organization provides a framework to understand how mRNP architecture could facilitate mRNA biogenesis and export.