Cytoplasmic regulatory functions of the KH-domain proteins hnRNPs K and E1/E2

A Ostareck-Lederer, DH Ostareck… - Trends in biochemical …, 1998 - cell.com
A Ostareck-Lederer, DH Ostareck, MW Hentze
Trends in biochemical sciences, 1998cell.com
410 nuclear shuttling (KNS) domain, also located between the proline-rich motifs and the
third KH domain25. The KNS domain confers the capacity for bi-directional transport across
the nuclear envelope on hnRNP K. It accesses an import pathway separate from those used
by the classical NLS and the M9 domain (the C-terminal 38-residue NLS of hnRNP A1).
Taken together, these findings suggest that hnRNP K is involved not only in nuclear RNA
processing but possibly also in nucleocytoplasmic transport and perhaps even in …
410 nuclear shuttling (KNS) domain, also located between the proline-rich motifs and the third KH domain25. The KNS domain confers the capacity for bi-directional transport across the nuclear envelope on hnRNP K. It accesses an import pathway separate from those used by the classical NLS and the M9 domain (the C-terminal 38-residue NLS of hnRNP A1). Taken together, these findings suggest that hnRNP K is involved not only in nuclear RNA processing but possibly also in nucleocytoplasmic transport and perhaps even in transcription. hnRNP E1 and hnRNP E2. The hnRNPs E1 and E2 share 80% homology. hnRNP E1 (GenBank accession number X78137) is identical to the recently described human poly (rC)-binding protein sub2. 3 (also known as PCBP-1 or ɑCP1) 5, 26, 27. hnRNP E2 (GenBank accession number X78136) is identical to human PCBP-2 (also known as ɑCP2) 5, 26. Both proteins lack other recognized RNA-binding motifs. In vitro, the hnRNP E1/E2 poly (rC)-binding activity, which can be inhibited by phosphorylation, has been assigned to the first and third KH domains9, 26 (Table I).
Unexpected cytoplasmic functions of hnRNPs K, E1 and E2 hnRNPs K and E1/E2 function as regulators of cytoplasmic mRNAs, particularly in erythroid cells. Reticulocyte 15-lipoxygenase (LOX) is a key enzyme in erythroid-cell differentiation. It catalyses the dioxygenation of intact phospholipids in mitochondrial membranes and participates in their breakdown in the final steps of erythrocyte maturation28. LOX mRNA, a highly abundant message in erythroid-precursor cells in the bone marrow, is translationally silenced until enucleated reticulocytes in the peripheral blood reach the final stages of maturation. A CU-rich repetitive sequence motif [known as the differentiation-control element (DICE)] in the 3! UTR of the LOX mRNA mediates this translational silencing6, 29. We purified two proteins that bind to this region from rabbit reticulocytes and identified them as hnRNP K and hnRNP E1 (Ref. 6). The proteins regulate translation of LOX mRNA specifically, through the DICE element (see Fig. 1 and Table I). Insertion of a 38-nucleotide synthetic DICE into the 3! UTR of a heterologous
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