EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6.

Li Zhou,Jin Hao,Qin Zhou,Yiman Li,Liyuan Huang,Zhicheng Liu,Rui Peng,Dongsheng Ni,Zhaomin Mao,Yue Yuan,Yaoshui Long,Honglian Wang,Zhongshi Lyu,Yao Du,Yuping Gu,Pan Ju,Jianing Liu

doi:10.3390/ijms17060811

Abstract

Apobec-1 complementation factor (A1CF) is a heterogeneous nuclear ribonuceloprotein (hnRNP) and mediates apolipoprotein-B mRNA editing. A1CF can promote the regeneration of the liver by post-transcriptionally stabilizing Interleukin-6 (IL-6) mRNA. It also contains two transcriptional variants-A1CF64 and A1CF65, distinguished by the appearance of a 24-nucleotide motif which contributes to the corresponding eight-amino acid motif of EIYMNVPV. For the first time, we demonstrated that the EIYMNVPV motif was essential for A1CF nucleus localization, A1CF deficient of the EIYMNVPV motif, A1CF (-8aa) showed cytoplasm distribution. More importantly, we found that A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. Furthermore, silencing of IL-6 attenuated A1CF (-8aa)-induced proliferation in MDA-MB-231 cells. In conclusion, notably, these findings suggest that A1CF (-8aa) promoted proliferation of MDA-MB-231 cells in vitro viewing IL-6 as a target. Thus, the EIYMNVPV motif could be developed as a potential target for basal-like breast cancer therapy.

Highlights

Apobec-1 complementation factor (A1CF), known as ACF, is the RNA binding subunit of a minimal core protein complex for apolipoprotein-B mRNA edition [1,2,3]
A1CF contains three non-identical RNA recognition motifs (RRM) in its N-terminus and a unique C-terminal auxiliary domain, which are required for complementing activity, RNA binding and apoB mRNA editing [12]
We demonstrated that the EIYMNVPV motif is essential for the nuclear localization of A1CF in MDCK cells and MDA-MB-231 cells

Summary

Introduction

Apobec-1 complementation factor (A1CF), known as ACF, is the RNA binding subunit of a minimal core protein complex for apolipoprotein-B (apoB) mRNA edition [1,2,3]. Coordinated with APOBEC-1, A1CF regulates site-specific C to U edition of apoB mRNA, leadings to the truncated isoform apoB48, rather than apoB100. During this process, A1CF recognizes an AU-rich motif (mooring sequences) on apoB mRNA and guides APOBEC-1, the cytosine deaminase, to localize to the right site to edit [1,4,5,6,7,8]. Dance et al demonstrated that the A1CF exon 11 is alternatively spliced to include or exclude 24 nucleotides at exon 12, leading to two variants, ACF65 and ACF64. Both variants are equivalent for apoB mRNA edition in cells [13]. Given the important role of RBM47 in progression of breast cancer, and similar structure, function between RBM47 and A1CF [15], we hypothesize that A1CF (-8aa) or A1CF may play a biological role in breast cancer

Methods

Results

Discussion

Conclusion