hnRNP A1 is a member of A/B subfamily of heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). hnRNP A1 is involved in the packaging of premature mRNA into hnRNP particles and transport of poly(A) mRNA from the nucleus to the cytoplasm. hnRNP A1 has been characterized as a component of protein complexes bound to premature mRNA (hnRNP complexes). hnRNP A1 is one of the most abundant and best-characterized components of hnRNP complexes. Human hnRNP functions also in telomere length regulation and miRNA biogenesis. It may play a role in the replication of RNA viruses.
Human hnRNP A1 consists of 320 amino acids. N-terminal region is composed of 2 RNA recognition motifs (RRM) followed by highly flexible C-terminal glycine-rich region. The structure of disordered C-terminal region which contains 45 % of glycine in its sequence has not been resolved till now. However, a short peptide from C-terminal region (residues 315 – 341) is available in the structure of transportin bound to hnRNP A1 (2H4M). and (together span residues 1 to 196) form .
The secondary structure of the RRM is characterized by a βαβαββαβ-fold in which the four β-strands make a flat anti-parallel β-sheet that forms most of the nucleic acid binding surface.
To date, several crystal structures of UP1 have been solved both in their free form and bound to repeats of telomeric DNA fragments. NMR structure of hnRNP A1 RRM domains was determined using a segmental labeling strategy [1].
Binding
Conservative resudues
Interaction between RRM domains
Two RRMs are interaction with one another via two Arg-Asp salt bridges. The interactions between domains of UP1 is quite week, since the orientation of the two RRMs can be influenced by nucleic acid binding or by contacts with neighboring molecules in the crystal lattice.
In the solution structure of free UP1, the two Arg-Asp salt bridges are conserved at the interface between RRM1 and RRM2.
