Deletion or mutation of the SMN1 (survival of motor neurons) gene causes the common, fatal neuromuscular disease spinal muscular atrophy. The SMN protein is important in small nuclear ribonucleoprotein (snRNP) assembly and interacts with snRNP proteins via arginine/glycine-rich domains. Recently, SMN was also found to interact with core protein components of the two major families of small nucleolar RNPs, fibrillarin and GAR1, suggesting that SMN may also function in the assembly of small nucleolar RNPs. Here we present results that indicate that the interaction of SMN with GAR1 is mediated by the Tudor domain of SMN. Single point mutations within the Tudor domain, including a spinal muscular atrophy patient mutation, impair the interaction of SMN with GAR1. Furthermore, we find that either of the two arginine/glycine-rich domains of GAR1 can provide for interaction with SMN, but removal of both results in loss of the interaction. Finally, we have found that unlike the interaction of SMN with the Sm snRNP proteins, interaction with GAR1 and fibrillarin is not enhanced by arginine dimethylation. Our results argue against post-translational arginine dimethylation as a general requirement for SMN recognition of proteins bearing arginine/glycine-rich domains.The best established role of SMN, the protein implicated in spinal muscular atrophy, is in the assembly of small nuclear RNA (snRNA) 1 -protein complexes that function in pre-mRNA splicing. SMN interacts with the common snRNP proteins Sm B/BЈ, D1 and D3, and LSm 4 through arginine/glycine (RG)-rich domains present in these proteins (1-4). Several studies have demonstrated that SMN and the other proteins of the SMN complex are required to facilitate the assembly of snRNPs and the generation of active spliceosomes (5-11).SMN appears to interact with a series of cellular proteins via a common mechanism that depends on the RG-rich domains in the target proteins (reviewed in Ref. 12). In addition to the Sm and LSm snRNP proteins, SMN has been found to interact with RNA helicase A (13), a protein associated with RNA polymerase II; coilin (14), the signature component of nuclear Cajal bodies; heteronuclear RNP binding proteins Q, R, and U (9, 15, 16); and fibrillarin and GAR1 (17, 18), core protein components of the Box C/D and Box H/ACA snoRNPs, respectively. Most of these proteins contain a single RG-rich region that has been shown to be essential for association with SMN. GAR1 has two RG-rich domains, and interestingly, it has been reported that both of these are necessary for interaction (18). Current evidence supports two different models for the basis of the interaction of SMN with partner proteins. One series of studies indicates that sequences near the carboxyl terminus of SMN mediate the interactions (including the interaction with GAR1) (2,11,13,16,18). This domain of SMN is important for the oligomerization of SMN (11,19,20). Other laboratories have implicated the Tudor domain of SMN in its interaction with some of the same RG domain proteins (3,4,7,14,17). ...

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BACKGROUND Physical activity (PA) preserves mobility, but few practices screen older adults for mobility impairment or counsel on PA. DESIGN “Promoting Active Aging” (PAA) was a mixed‐methods randomized‐controlled pilot, to test the feasibility and acceptability of a video‐based PA counseling tool and implementation into practice of two mobility assessment tools. SETTING Three primary care practices affiliated with Wake Forest Baptist Health. PARTICIPANTS Adults aged 65 years and older who presented for primary care follow‐up and were willing and able to answer self‐report questions and walk 4 meters (n = 59). INTERVENTION Video‐based PA counseling intervention versus control video, “Healthy Eating.” MEASUREMENTS Potential participants completed mobility assessments: self‐report (Mobility Assessment Tool‐short form (MAT‐sf)) and performance based (4‐meter walk test). We assessed PAAʼs implementation—feasibility, acceptability, and value—via interviews and surveys. Effectiveness was measured via participant attendance at a PA information session. RESULTS Of 92 patients approached, 89 (96.7%) agreed to mobility assessment. Eighty‐nine completed MAT‐sf, and 97.8% (87/89) completed 4‐meter walk test. Sixty‐seven (75%) met eligibility criteria, and 59 (88%) consented to be randomized either to the PA counseling intervention (Video‐PA) or to active control (Video‐C). Most participants viewed the walk test positively (51/59; 86.4%). Staff reported that completion of patient surveys, MAT‐sf, and videos required significant staff time and support (median = 26 minutes for all), resulting in low acceptability of MAT‐sf and the videos. Attendance at a PA information session did not differ by randomization group (Video‐PA = 11/29 (37.9%); Video‐C = 12/30 (40%); 95% confidence interval for difference in proportion = −0.29 to 0.25). CONCLUSIONS Mobility assessment, particularly a 4‐meter walk test, was feasible in primary care. Tablet‐based assessment (MAT‐sf) and video counseling tools, selected to reduce staff effort, instead required significant time to implement. Future work to promote PA should identify effective ways to facilitate adoption of PA in sedentary older adults that do not burden staff.