231 tRNA derived fragments(tRFs) regulate oxidative phosphorylation to participate in SLE pathogenesis

Background tRNA derived fragments(tRFs) are 18 to 40-nucleotide(nt) small RNAs cleaved from mature tRNAs or precursor tRNA transcripts. There is growing evidence that tRFs play important roles in cellular homeostasis. This study focused on abnormal expression of tRFs in CD4 +T lymphocytes from SLE patients, their function on regulation of oxidative metabolism and potential roles in development of systemic lupus erythematosus (SLE). Methods CD4 +T lymphocytes isolated from 97 SLE patients, 30 RA patients, 10 AS patients and 20 healthy donors were used in our in vitro experiments. Total RNA of CD4 +T lymphocytes isolated from 4 SLE patients and 3 healthy donors were used to perform small RNA sequencing. Total RNA of CD4 +T lymphocytes transfected with synthetic tRF-3009 or negative control (a random sequence, single strand) were used to perform next generation sequencing. CD4 +T lymphocytes isolated from healthy donors were transfected with tRF-3009/negative control or tRF-3009 siRNA/si-NC in vitro, with/without IFN-alpha treatment, to analyze OCRROS and ATP concentration. Real-time qRT-PCR was performed to analyze expression of tRF-3009 and related gene expressions. Results We have identified a series of tRFs expressed abnormally in SLE CD4 +T lymphocytes. Interestingly, almost all up regulated tRFs were from 3end of mature tRNA while down regulated ones were from 3end of tRNA precursors. We have found that expression of tRF-3009 was corelated with lupus nephritis (LN) and urine protein (PRO). The expression of tRF-3009 could be induced by IFN-alpha treatment in vitro. Knockdown of tRF-3009 by siRNA could rescue the metabolism change of CD4 +T lymphocytes induced by IFN-alpha. Transfection of tRF-3009 alone could up regulate oxidative phosphorylation of CD4 +T lymphocytes in vitro. Conclusions This study identified a series of abnormally expressed tRFs existed in CD4 +T lymphocytes isolated from SLE patients. One of these small RNAs, tRF-3009 also enriched in kidney and corelated with occurrence of lupus nephritis. tRF-3009 anticipated in metabolism regulation, may play important roles in SLE pathogenesis. Funding Source(s): The National Key Research and Development Program of China(2016YFC0903900 and 2017YFC0909000)