Abstract
FAM46A belongs to the FAM46 subfamily of the nucleotidyltransferase-fold superfamily and is predicted to be a non-canonical poly(A) polymerase. FAM46A has been linked to several human disorders including retinitis pigmentosa, bone abnormality, cancer, and obesity. However, its molecular and functional characteristics are largely unknown. We herein report that FAM46A is expressed in cells of the hematopoietic system and plays a role in hemin-induced hemoglobinization. FAM46A is a nucleocytoplasmic shuttle protein modified by Tyr-phosphorylation only in the cytosol, where it is closely associated with ER. On the other hand, it is located proximal to the chromatin regions of active transcription in the nucleus. FAM46A is a cell cycle-dependent poly-ubiquitinated short-lived protein degraded mostly by proteasome and its overexpression inhibits cell growth and promotes hemin-induced hemoglobinization in K562 cell. Site-directed mutagenesis experiments confirm the non-canonical poly(A) polymerase activity of FAM46A is essential for enhanced hemin-induced hemoglobinization. In summary, FAM46A is a novel poly(A) polymerase that functions as a critical intracellular modulator of hemoglobinization.
Highlights
Human chromosome 6 is known to harbor numerous genetic hotspots for retinal diseases such as retinitis pigmentosa (RP) (Small et al, 1992; Stone et al, 1994; Kelsell et al, 1998; Ruiz et al, 1998; Dharmaraj et al, 2000; Kniazeva et al, 2000)
Fam46a expression was found to be up-regulated during the terminal differentiation and maturation of the MEL mouse erythroid cell line (Figure 1B)
These results suggest that family-with-sequence-similarity 46 member A (FAM46A) might play a functional role in myeloid cells and differentiation of erythroid cells
Summary
Human chromosome 6 is known to harbor numerous genetic hotspots for retinal diseases such as RP (Small et al, 1992; Stone et al, 1994; Kelsell et al, 1998; Ruiz et al, 1998; Dharmaraj et al, 2000; Kniazeva et al, 2000). One novel candidate disease gene is C6orf, which is mapped within the autosomal recessive RP25 locus on chromosome 6q14 and expressed in the retina (Lagali et al, 2002; Barragan et al, 2008). Mouse Fam46a was detected in the developing tooth buds, localized in the nucleus, and interacted with the ZFYVE9 protein (Colland et al, 2004; Etokebe et al, 2009). It seems that FAM46A is a multifunctional intracellular protein distributed both in the cytosolic and nuclear compartments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
