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. Overall design: 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.