## 1 Introduction  
Spinal Muscular Atrophy (SMA) is a neuromuscular disease characterized by loss of motoneurons in the brain stem and spinal cord and caused by deletion or mutation of the survival of motoneuron 1(_SMN1_) gene [1]. The _SMN2_ gene is highly similar but contains mutations leading to exclusion of exon 7 during pre-mRNA splicing [2]. The resulting truncated protein is unstable and cannot rescue the loss of _SMN1_[2; 3]. As a consequence, muscle denervation at motor endplates is increased, leading to progressive muscle denervation, weakness, and atrophy [4]. The most severe form is SMA type I with an early onset before 6 months and a life expectancy smaller than two years. Copy number variation of _SMN2_ can increase the amount of functional SMN protein [5] and leads to milder forms of the disease (SMA types II, III, and IV). Therapies have been approved very recently that include splicing correction of _SMN2_ by an antisense-based approach and gene replacement therapy by systemic administration of an adeno-associated virus (AAV9) system coding for full-length SMN [6; 7; 8]. Although the results of these therapies are very impressive, there is a need for combinatorial approaches to further improve clinical outcomes. Moreover, the molecular pathmechanisms of SMA are still elusive. The SMN protein is involved in a broad spectrum of molecular interactions [9]. The best-characterized function is its involvement in the biogenesis of small nuclear ribonucleoproteins (snRNPs). The so-called SMN complex (comprising its core components SMN, Gemins2-8 and unrip) promotes the ring-shaped assembly of the seven Sm proteins together with a U-rich small nuclear RNA (snRNA) [10; 11; 12; 13]. After the cytoplasmic assembly of the pre-snRNP, the SMN complex guides it to distinct nuclear structures (Cajal bodies, CBs, or gems) for their maturation and release of mature tri-snRNPs [14]. Moreover, the redistribution of SMN from the cytoplasm into nuclear bodies is mediated by interaction of SMN with zinc finger protein ZPR1 in serum-induced response [15]. This ZPR1-driven translocation of SMN is disordered in SMA type I patients [15]. SMN is involved in a number of other cellular functions such as regulation of the neuronal actin cytoskeleton, signaling, and DNA repair [16; 17; 18; 19]. However, less is known about the role of post-translational regulation on cellular functions of SMN. Post-translational modifications such as phosphorylation regulate the function of SMN in a compartment-specific manner [20; 21; 22; 23; 24; 25]. However, only little is known about the specific kinases and phosphatases acting on SMN and modulating its functional properties. For example, phosphorylation by protein kinase A (PKA) accelerates SMN accumulation in SMN-complexes as well as increases its binding to Gemin2 and Gemin8 and its stability [20; 26; 27], whereas dephosphorylation by the nuclear phosphatase PPM1G/PP2C\(\gamma\) leads to accumulation of the SMN complex in CBs [21]. Importantly, several phosphorylation sites at the N-terminus regulate SMN protein stability, self-oligomerization, and the cytosolic assembly of the SMN complex [24]. Nonetheless, to the best of our knowledge, there are no studies showing functionality of the putative C-terminal phosphorylation sites as the C-terminal sequence renders SMN inaccessible for proteinases typically used in mass spectrometry (MS) analysis. Amongst other cellular phenotypes, SMA motoneurons show a reduction of SMN-positive nuclear bodies (NBs). Thus, the understanding of post-translational modifications of SMN is also important for the development of combinatorial SMA treatments. A therapeutic strategy that improves SMN stability could enhance the benefits of approaches increasing SMN expression. In this context, we aimed to determine C-terminal phosphorylation sites and study their physiological functions. Here, we describe two novel phosphorylation sites, namely SMN S290 and S292.