Adenosine-to-inosine (A-to-I) RNA editing is the most common posttranscriptional editing to create somatic mutations and increase proteomic diversity. However, the functions of the edited mutations are largely underexplored. To identify novel targets in lung adenocarcinoma (LUAD), we conducted a genome-wide somatic A-to-I RNA editing analysis of 23 paired adjacent normal and LUAD transcriptomes and identified 26,280 events, including known nonsynonymous AZIN1-S367G and novel RHOAiso2 (RHOA isoform 2)-R176G, tubulin gamma complex associated protein 2 (TUBGCP2)-N211S, and RBMXL1-I40 M mutations. We validated the edited mutations in silico in multiple databases and in newly collected LUAD tissue pairs with the SEQUENOM MassARRAY ® and TaqMan PCR Systems. We selected RHOAiso2-R176G due to its significant level, isoform-specificity, and being the most common somatic edited nonsynonymous mutation of RHOAiso2 to investigate its roles in LUAD tumorigenesis. RHOAiso2 is a ubiquitous but low-expression alternative spliced isoform received a unique Alu-rich exon at the 3′ RHOA mRNA to become an editing RNA target, leading to somatic hypermutation and protein

A protein expression is regulated by transcription, translation, and sequential processing. However, well-correlated RNA and protein abundance just only proportionate 40%, and even poorer when the cell was stressed, differentiated, or tumorigenic transformed. Here, we discovered spermatocyte (SP) differentiated to round spermatid (RS) had equal regulation extent between transcription and translation which may related to ribosomal behavior alteration. The change of ribosome occupancy was related to SP and RS specific function in spermatogenesis. Interactome of the functional ribosome in SP and RS revealed the activated ribosome in SP but stalled and nonsense-mediated decay (NMD) associated functional ribosome in RS. RS functional ribosomes occupied 5'UTR of SP specific transcripts and correlated its' RNA and protein downregulation. These findings suggested a branched NMD pathway was activated in RS to eliminate SP specific transcripts and keep them from being translated. Our discovery suggested the heterogeneity of ribosomal interactome may play an important role in spermatogenesis.