The PSI–U1 snRNP interaction regulates male mating behavior in Drosophila

Abstract

Alternative pre-mRNA splicing (AS) is a critical regulatory mechanism that operates extensively in the nervous system to produce diverse protein isoforms. Fruitless AS isoforms have been shown to influence male courtship behavior, but the underlying mechanisms are unknown. Using genome-wide approaches and quantitative behavioral assays, we show that the P-element somatic inhibitor (PSI) and its interaction with the U1 small nuclear ribonucleoprotein complex (snRNP) control male courtship behavior. PSI mutants lacking the U1 snRNP-interacting domain (PSIΔAB mutant) exhibit extended but futile mating attempts. The PSIΔAB mutant results in significant changes in the AS patterns of ∼1,200 genes in the Drosophila brain, many of which have been implicated in the regulation of male courtship behavior. PSI directly regulates the AS of at least one-third of these transcripts, suggesting that PSI-U1 snRNP interactions coordinate the behavioral network underlying courtship behavior. Importantly, one of these direct targets is fruitless, the master regulator of courtship. Thus, PSI imposes a specific mode of regulatory control within the neuronal circuit controlling courtship, even though it is broadly expressed in the fly nervous system. This study reinforces the importance of AS in the control of gene activity in neurons and integrated neuronal circuits, and provides a surprising link between a pleiotropic pre-mRNA splicing pathway and the precise control of successful male mating behavior.PSI | U1 snRNP | alternative pre-mRNA splicing | male courtship behavior H ow gene regulation modulates neuronal activities leading to cognition and behavior is an important question in biology. Although many behavior-associated genes and neuronal cell types have been identified, a detailed understanding that links the molecular events of gene regulation to specific behaviors is still lacking. Alternative pre-mRNA splicing (AS) is a crucial gene regulatory mechanism that enables a single gene to generate functionally distinct messenger RNA transcripts (mRNAs) and protein products (1). The nervous system makes extensive use of AS to generate diverse and complex neural mRNA expression patterns that determine numerous neuronal cell types and functions (2). AS is regulated by the small nuclear ribonucleoprotein complexes (snRNPs) that compose the spliceosome for intron recognition and removal, as well as a large repertoire of non-snRNP RNA-binding proteins that affect decisions on splice site use (3). This dynamic and complex AS regulatory network modulates diverse neuronal functions, like synaptic transmission and signal processing, hence further impacting higher brain functions, such as cognition and behavioral control (4).The Drosophila KH-domain RNA binding splicing factor P-element somatic inhibitor (PSI) is best known for regulating tissue-specific AS of the Drosophila P-element transposon transcripts to restrict transposition activity to germ-line tissues (5, 6). PSI directly interacts with the U1 snRNP through a 70-aa tandem direct ...

piRNA-mediated regulation of transposon alternative splicing in the soma and germ line

“…Genome-wide analysis of differentially spliced mRNAs was performed using the Junction Usage Model (JUM) package 44,45 (https://github.com/qqwang-berkeley/JUM; version 1.3.2) with default parameters and following the JUM manual. Briefly, RNA-seq data were mapped to the Drosophila genome (dm3) using STAR 46 in two-pass mode, following instructions in the STAR manual (https://github.com/alexdobin/STAR).…”

Transcriptional repression of Myc underlies AGO1’s tumour suppressor function

“…Like FUBP1, Psi also interacts with RNA Pol II transcriptional machinery, particularly the transcriptional Mediator (MED) complex, to pattern Myc transcription, cell and tissue growth in the Drosophila wing epithelium (Guo et al, 2016). In addition to roles in transcription, Psi binds RNA via the KH domains and interacts with the spliceosome to regulate mRNA splicing (Labourier et al, 2001;Wang et al, 2016). Although Co-IP Mass Spectrometry detected Psi in complex with the Argonaute protein, AGO1 (Guo et al, 2016), the potential significance of this interaction is unknown.…”

FUBP/KH domain proteins in transcription: Back to the future

“…42 Indeed, subsequent studies revealed broader roles for Psi in pre-mRNA splicing, including for many genes required for male courtship behavior. 43 Further to these RNA processing functions, and in accordance with Psi behaving in a functionally analogous manner to FUBP1, recent studies revealed a key role for Psi in sustaining developmentally regulated MYC transcription and, thus, cell and tissue growth. 5 Moreover, like FUBP1, 44 Psi has potent transcriptional activator capacity in vitro, mediated by conserved tyrosine-rich domains (YM1 and YM2 repeats).…”