Novel function of U7 snRNA in the repression of HERV1/LTR12s and lincRNAs in human cells

U7 snRNA is part of the U7 snRNP complex, required for the 3' end processing of replication-dependent histone pre-mRNAs in S phase of the cell cycle. Here, we show that U7 snRNA plays another function in inhibiting the expression of a subset of human endogenous retroviruses of HERV1/LTR12 class and LTR12-containing long intergenic noncoding RNAs (lincRNAs), both bearing sequence motifs that perfectly match the 5’ end of U7 snRNA. We demonstrate that U7 snRNA inhibits HERV1/LTR12 and lincRNA transcription and propose a mechanism in which U7 snRNA hampers the binding/activity of the NF-Y transcription factor to CCAAT motifs within LTR12 elements. Thereby, U7 snRNA plays a protective role in maintaining the silencing of deleterious genetic elements in selected types of cells. In turn, the expression of U7-dependent HERV1/LTR12s and lincRNAs seems to be relevant during early spermatogenesis in testis, where their synthesis is highly upregulated. To investigate novel functions of U7 snRNA in human cells, we depleted U7 snRNA using a chimeric antisense oligonucleotide (ASO) in HEK293T cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 biological replicates of HEK293T transfected with the control ASO or ASO targeting U7 snRNA.