sisRNAs engage with their hosts

Pek et al. describe how a stable, intron-derived RNA regulates the expression of its host gene during Drosophila embryogenesis.

Once they are spliced out of nascent mRNAs, noncoding intron sequences are usually degraded rapidly. At least in Xenopus eggs and human cell lines, however, some intronic RNAs persist for long periods, although the function of these stable intronic sequence (sis) RNAs remains unknown. Pek et al. used deep sequencing to look for sisRNAs in newly fertilized Drosophila embryos, whose initial development depends on a pool of stable RNA generated several hours earlier during oogenesis.

The researchers identified over 30 candidate sisRNAs, including one, dubbed sisR-1, that was derived from the fourth intron of a gene called rga. After being spliced out of the rga pre-mRNA, sisR-1 was processed into longer and shorter versions that localized to the nucleus and cytoplasm, respectively. Structural predictions suggested that the 3′ region of nuclear sisR-1 is exposed and available to base pair with an antisense transcript, named ASTR, that is also produced from the rga locus.

Pek et al. discovered that ASTR promoted transcription of the rga gene in early embryos, causing sisR-1 to gradually accumulate until, later in development, it was able to suppress ASTR and shut down rga expression. Knocking down sisR-1 delayed the down-regulation of ASTR and rga, but otherwise embryogenesis proceeded normally. Senior author Jun Wei Pek now wants to investigate how sisR-1 is stabilized, and whether its knockdown affects fly development in sensitized genetic backgrounds.